Current state of Alzheimer’s fluid biomarkers

1.

Agnello L, Bivona G, Novo G, Scazzone C, Muratore R, Levantino P et al (2017) Heart-type fatty acid binding protein is a sensitive biomarker for early AMI detection in troponin negative patients: a pilot study. Scand J Clin Lab Invest 77:428–432. https://doi.org/10.1080/00365513.2017.1335880 CrossRefPubMed

2.

Alcolea D, Martínez-Lage P, Sánchez-Juan P, Olazáran J, Antúnez C, Izagirre A et al (2015) Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology 85:626–633. https://doi.org/10.1212/wnl.0000000000001859 CrossRefPubMed

3.

Alcolea D, Vilaplana E, Pegueroles J, Montal V, Sánchez-Juan P, González-Suárez A et al (2015) Relationship between cortical thickness and cerebrospinal fluid YKL-40 in predementia stages of Alzheimer’s disease. Neurobiol Aging 36:2018–2023. https://doi.org/10.1016/j.neurobiolaging.2015.03.001 CrossRefPubMed

4.

Alcolea D, Vilaplana E, Suárez-Calvet M, Illán-Gala I, Blesa R, Clarimón J et al (2017) CSF sAPPβ, YKL-40, and neurofilament light in frontotemporal lobar degeneration. Neurology 89:178–188. https://doi.org/10.1212/WNL.0000000000004088 CrossRefPubMed

5.

Alexopoulos P, Werle L, Roesler J, Thierjung N, Gleixner LS, Yakushev I et al (2016) Conflicting cerebrospinal fluid biomarkers and progression to dementia due to Alzheimer’s disease. Alzheimers Res Ther 8:51. https://doi.org/10.1186/s13195-016-0220-z CrossRefPubMedPubMedCentral

6.

Association Alzheimer’s (2016) Alzheimer’s disease facts and figures. Alzheimers Dement 12:459–509CrossRef

7.

Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445. https://doi.org/10.1002/ana.21154 CrossRefPubMedPubMedCentral

8.

Anand S, Barnes JM, Young SA, Garcia DM, Tolley HD, Kauwe JSK et al (2017) Discovery and confirmation of diagnostic serum lipid biomarkers for Alzheimer’s disease using direct infusion mass spectrometry. J Alzheimers Dis 59:277–290. https://doi.org/10.3233/JAD-170035 CrossRefPubMed

9.

Andreasen N, Minthon L, Vanmechelen E, Vanderstichele H, Davidsson P, Winblad B et al (1999) Cerebrospinal fluid tau and Aβ42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment. Neurosci Lett 273:5–8CrossRefPubMed

10.

Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S et al (1995) Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 182:155–162CrossRefPubMed

11.

Antonell A, Mansilla A, Rami L, Lladó A, Iranzo A, Olives J et al (2014) Cerebrospinal fluid level of YKL-40 protein in preclinical and prodromal Alzheimer’s disease. J Alzheimers Dis 42:901–908. https://doi.org/10.3233/jad-140624 CrossRefPubMed

12.

Arnerić SP, Batrla-Utermann R, Beckett L, Bittner T, Blennow K, Carter L et al (2017) Cerebrospinal fluid biomarkers for Alzheimer’s disease: a view of the regulatory science qualification landscape from the Coalition Against Major Diseases CSF Biomarker Team. J Alzheimers Dis 55:19–35. https://doi.org/10.3233/JAD-160573 CrossRefPubMed

13.

Ayton S, Diouf I, Bush AI, Alzheimer’s Disease Neuroimaging Initiative (2017) Evidence that iron accelerates Alzheimer’s pathology: a CSF biomarker study. J Neurol Neurosurg Psychiatry 89:456–460. https://doi.org/10.1136/jnnp-2017-316551 CrossRefPubMed

14.

Ayton S, Faux NG, Bush AI (2017) Association of cerebrospinal fluid ferritin level with preclinical cognitive decline in APOE-ɛ4 carriers. JAMA Neurol 74:122–125. https://doi.org/10.1001/jamaneurol.2016.4406 CrossRefPubMed

15.

Ayton S, Faux NG, Bush AI, Alzheimer’s Disease Neuroimaging Initiative (2015) Ferritin levels in the cerebrospinal fluid predict Alzheimer’s disease outcomes and are regulated by APOE. Nat Commun 6:6760. https://doi.org/10.1038/ncomms7760 CrossRefPubMed

16.

Ayton S, Fazlollahi A, Bourgeat P, Raniga P, Ng A, Lim YY et al (2017) Cerebral quantitative susceptibility mapping predicts amyloid-beta-related cognitive decline. Brain 140:2112–2119. https://doi.org/10.1093/brain/awx137 CrossRefPubMed

17.

Babić Leko M, Borovečki F, Dejanović N, Hof PR, Ŝimić G (2016) Predictive value of cerebrospinal fluid visinin-like protein-1 levels for Alzheimer’s disease early detection and differential diagnosis in patients with mild cognitive impairment. J Alzheimers Dis 50:765–778. https://doi.org/10.3233/jad-150705 CrossRefPubMed

18.

Bachurin SO, Bovina EV, Ustyugov AA (2017) Drugs in clinical trials for Alzheimer’s disease: the major trends. Med Res Rev 37:1186–1225. https://doi.org/10.1002/med.21434 CrossRefPubMed

19.

Bakota L, Brandt R (2016) Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs 76:301–313. https://doi.org/10.1007/s40265-015-0529-0 CrossRefPubMedPubMedCentral

20.

Baldacci F, Lista S, Cavedo E, Bonuccelli U, Hampel H (2017) Diagnostic function of the neuroinflammatory biomarker YKL-40 in Alzheimer’s disease and other neurodegenerative diseases. Expert Rev Proteom 14:285–299. https://doi.org/10.1080/14789450.2017.1304217 CrossRef

21.

Baldacci F, Lista S, Garaci F, Bonuccelli U, Toschi N, Hampel H (2016) Biomarker-guided classification scheme of neurodegenerative diseases. J Sport Health Sci 5:383–387CrossRefPubMedPubMedCentral

22.

Baldacci F, Lista S, O’Bryant SE, Ceravolo R, Toschi N, Hampel H et al (2018) Blood-based biomarker screening with agnostic biological definitions for an accurate diagnosis within the dimensional spectrum of neurodegenerative diseases. Methods Mol Biol 1750:139–155. https://doi.org/10.1007/978-1-4939-7704-8_9 CrossRefPubMed

23.

Baldacci F, Toschi N, Lista S, Zetterberg H, Blennow K, Kilimann I et al (2017) Two-level diagnostic classification using cerebrospinal fluid YKL-40 in Alzheimer’s disease. Alzheimers Dement 13:993–1003. https://doi.org/10.1016/j.jalz.2017.01.021 CrossRefPubMed

24.

Ballatore C, Brunden KR, Trojanowski JQ, Lee VM, Smith AB 3rd (2017) Non-naturally occurring small molecule microtubule-stabilizing agents: a potential tactic for CNS-directed therapies. ACS Chem Neurosci 8:5–7. https://doi.org/10.1021/acschemneuro.6b00384 CrossRefPubMed

25.

Bayer TA, Wirths O (2014) Focusing the amyloid cascade hypothesis on N-truncated Abeta peptides as drug targets against Alzheimer’s disease. Acta Neuropathol 127:787–801. https://doi.org/10.1007/s00401-014-1287-x CrossRefPubMedPubMedCentral

26.

Begcevic I, Brinc D, Brown M, Martinez-Morillo E, Goldhardt O, Grimmer T et al (2018) Brain-related proteins as potential CSF biomarkers of Alzheimer’s disease: a targeted mass spectrometry approach. J Proteom 182:12–20. https://doi.org/10.1016/j.jprot.2018.04.027 CrossRef

27.

Berge G, Sando SB, Albrektsen G, Lauridsen C, Møller I, Grøntvedt GR et al (2016) Alpha-synuclein measured in cerebrospinal fluid from patients with Alzheimer’s disease, mild cognitive impairment, or healthy controls: a two year follow-up study. BMC Neurol 16:180. https://doi.org/10.1186/s12883-016-0706-0 CrossRefPubMedPubMedCentral

28.

Bergman J, Dring A, Zetterberg H, Blennow K, Norgren N, Gilthorpe J et al (2016) Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol Neuroimmunol Neuroinflamm 3:e271. https://doi.org/10.1212/NXI.0000000000000271 CrossRefPubMedPubMedCentral

29.

Bettcher BM, Johnson SC, Fitch R, Casaletto KB, Heffernan KS, Asthana S et al (2018) Cerebrospinal fluid and plasma levels of inflammation differentially relate to CNS markers of Alzheimer’s disease pathology and neuronal damage. J Alzheimers Dis 62:385–397. https://doi.org/10.3233/JAD-170602 CrossRefPubMedPubMedCentral

30.

Blennow K, Bogdanovic N, Alafuzoff I, Ekman R, Davidsson P (1996) Synaptic pathology in Alzheimer’s disease: relation to severity of dementia, but not to senile plaques, neurofibrillary tangles, or the ApoE4 allele. J Neural Transm (Vienna) 103:603–618. https://doi.org/10.1007/BF01273157 CrossRef

31.

Blennow K, De Meyer G, Hansson O, Minthon L, Wallin A, Zetterberg H et al (2009) Evolution of Abeta42 and Abeta40 levels and Abeta42/Abeta40 ratio in plasma during progression of Alzheimer’s disease: a multicenter assessment. J Nutr Health Aging 13:205–208CrossRefPubMed

32.

Blennow K, Dubois B, Fagan AM, Lewczuk P, de Leon MJ, Hampel H (2015) Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease. Alzheimers Dement 11:58–69. https://doi.org/10.1016/j.jalz.2014.02.004 CrossRefPubMed

33.

Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6:131–144. https://doi.org/10.1038/nrneurol.2010.4 CrossRefPubMed

34.

Blennow K, Zetterberg H, Minthon L, Lannfelt L, Strid S, Annas P et al (2007) Longitudinal stability of CSF biomarkers in Alzheimer’s disease. Neurosci Lett 419:18–22. https://doi.org/10.1016/j.neulet.2007.03.064 CrossRefPubMed

35.

Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ (2015) Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci 16:109–120. https://doi.org/10.1038/nrn3887 CrossRefPubMedPubMedCentral

36.

Brinkmalm A, Brinkmalm G, Honer WG, Frölich L, Hausner L, Minthon L et al (2014) SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer’s disease. Mol Neurodegener 9:53. https://doi.org/10.1186/1750-1326-9-53 CrossRefPubMedPubMedCentral

37.

Bronzuoli MR, Iacomino A, Steardo L, Scuderi C (2016) Targeting neuroinflammation in Alzheimer’s disease. J Inflamm Res 9:199–208. https://doi.org/10.2147/JIR.S86958 CrossRefPubMedPubMedCentral

38.

Brosseron F, Traschutz A, Widmann CN, Kummer MP, Tacik P, Santarelli F et al (2018) Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer’s disease. Alzheimers Res Ther 10:25. https://doi.org/10.1186/s13195-018-0353-3 CrossRefPubMedPubMedCentral

39.

Bruggink KA, Kuiperij HB, Claassen JA, Verbeek MM (2013) The diagnostic value of CSF amyloid-beta(43) in differentiation of dementia syndromes. Curr Alzheimer Res 10:1034–1040CrossRefPubMed

40.

Brunden KR, Zhang B, Carroll J, Yao Y, Potuzak JS, Hogan AM et al (2010) Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy. J Neurosci 30:13861–13866. https://doi.org/10.1523/jneurosci.3059-10.2010 CrossRefPubMedPubMedCentral

41.

Buchhave P, Blennow K, Zetterberg H, Stomrud E, Londos E, Andreasen N, Minthon L et al (2009) Longitudinal study of CSF biomarkers in patients with Alzheimer’s disease. PLoS One 4:e6294. https://doi.org/10.1371/journal.pone.0006294 CrossRefPubMedPubMedCentral

42.

Budd Haeberlein S, O’Gorman J, Chiao P, Bussiere T, von Rosenstiel P, Tian Y et al (2017) Clinical development of aducanumab, an anti-Abeta human monoclonal antibody being investigated for the treatment of early Alzheimer’s disease. J Prev Alzheimers Dis 4:255–263. https://doi.org/10.14283/jpad.2017.39 CrossRefPubMed

43.

Byrne LM, Rodrigues FB, Blennow K, Durr A, Leavitt BR, Roos RAC et al (2017) Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysis. Lancet Neurol 16:601–609. https://doi.org/10.1016/s1474-4422(17)30124-2 CrossRefPubMedPubMedCentral

44.

Calsolaro V, Edison P (2016) Neuroinflammation in Alzheimer’s disease: current evidence and future directions. Alzheimers Dement 12:719–732. https://doi.org/10.1016/j.jalz.2016.02.010 CrossRefPubMed

45.

Carroll CM, Li YM (2016) Physiological and pathological roles of the γ-secretase complex. Brain Res Bull 126:199–206. https://doi.org/10.1016/j.brainresbull.2016.04.019 CrossRefPubMedPubMedCentral

46.

Castrillo JI, Lista S, Hampel H, Ritchie CW (2018) Systems biology methods for Alzheimer’s disease research toward molecular signatures, subtypes, and stages and precision medicine: application in cohort studies and trials. Methods Mol Biol 1750:31–66. https://doi.org/10.1007/978-1-4939-7704-8_3 CrossRefPubMed

47.

Catafau AM, Bullich S (2017) Non-amyloid PET imaging biomarkers for neurodegeneration: focus on tau, alpha-synuclein and neuroinflammation. Curr Alzheimer Res 14:169–177CrossRefPubMed

48.

Chakraborty A, de Wit NM, van der Flier WM, de Vries HE (2017) The blood brain barrier in Alzheimer’s disease. Vascul Pharmacol 89:12–18. https://doi.org/10.1016/j.vph.2016.11.008 CrossRefPubMed

49.

Chang KA, Shin KY, Nam E, Lee YB, Moon C, Suh YH et al (2016) Plasma soluble neuregulin-1 as a diagnostic biomarker for Alzheimer’s disease. Neurochem Int 97:1–7. https://doi.org/10.1016/j.neuint.2016.04.012 CrossRefPubMed

50.

Chang XL, Tan MS, Tan L, Yu JT (2016) The role of TDP-43 in Alzheimer’s disease. Mol Neurobiol 53:3349–3359. https://doi.org/10.1007/s12035-015-9264-5 CrossRefPubMed

51.

Chen-Plotkin AS, Lee VM, Trojanowski JQ (2010) TAR DNA-binding protein 43 in neurodegenerative disease. Nat Rev Neurol 6:211–220. https://doi.org/10.1038/nrneurol.2010.18 CrossRefPubMedPubMedCentral

52.

Chen Z, Trapp BD (2016) Microglia and neuroprotection. J Neurochem 136(Suppl 1):10–17. https://doi.org/10.1111/jnc.13062 CrossRefPubMed

53.

Chiasserini D, Biscetti L, Eusebi P, Salvadori N, Frattini G, Simoni S et al (2017) Differential role of CSF fatty acid binding protein 3, α-synuclein, and Alzheimer’s disease core biomarkers in Lewy body disorders and Alzheimer’s dementia. Alzheimers Res Ther 9:52. https://doi.org/10.1186/s13195-017-0276-4 CrossRefPubMedPubMedCentral

54.

Choi J, Lee HW, Suk K (2011) Plasma level of chitinase 3-like 1 protein increases in patients with early Alzheimer’s disease. J Neurol 258:2181–2185. https://doi.org/10.1007/s00415-011-6087-9 CrossRefPubMed

55.

Cornett CR, Markesbery WR, Ehmann WD (1998) Imbalances of trace elements related to oxidative damage in Alzheimer’s disease brain. Neurotoxicology 19:339–345PubMed

56.

Corso G, Cristofano A, Sapere N, la Marca G, Angiolillo A, Vitale M et al (2017) Serum amino acid profiles in normal subjects and in patients with or at risk of Alzheimer dementia. Dement Geriatr Cogn Dis Extra 7:143–159. https://doi.org/10.1159/000466688 CrossRefPubMedPubMedCentral

57.

Craig-Schapiro R, Perrin RJ, Roe CM, Xiong C, Carter D, Cairns NJ et al (2010) YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry 68:903–912. https://doi.org/10.1016/j.biopsych.2010.08.025 CrossRefPubMedPubMedCentral

58.

Cristóvão JS, Santos R, Gomes CM (2016) Metals and neuronal metal binding proteins implicated in Alzheimer’s disease. Oxid Med Cell Longev 2016:9812178. https://doi.org/10.1155/2016/9812178 CrossRefPubMedPubMedCentral

59.

Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM et al (2013) GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer’s disease. Neuron 78:256–268. https://doi.org/10.1016/j.neuron.2013.02.026 CrossRefPubMedPubMedCentral

60.

Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K (2017) Alzheimer’s disease drug development pipeline: 2017. Alzheimers Dement (N Y) 3:367–384. https://doi.org/10.1016/j.trci.2017.05.002 CrossRef

61.

Dage JL, Wennberg AM, Airey DC, Hagen CE, Knopman DS, Machulda MM et al (2016) Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort. Alzheimers Dement 12:1226–1234. https://doi.org/10.1016/j.jalz.2016.06.001 CrossRefPubMedPubMedCentral

62.

Davidsson P, Blennow K (1998) Neurochemical dissection of synaptic pathology in Alzheimer’s disease. Int Psychogeriatr 10:11–23CrossRefPubMed

63.

De Vos A, Jacobs D, Struyfs H, Fransen E, Andersson K, Portelius E et al (2015) C-terminal neurogranin is increased in cerebrospinal fluid but unchanged in plasma in Alzheimer’s disease. Alzheimers Dement 11:1461–1469. https://doi.org/10.1016/j.jalz.2015.05.012 CrossRefPubMed

64.

De Vos A, Struyfs H, Jacobs D, Fransen E, Klewansky T, De Roeck E et al (2016) The cerebrospinal fluid neurogranin/BACE1 ratio is a potential correlate of cognitive decline in Alzheimer’s disease. J Alzheimers Dis 53:1523–1538. https://doi.org/10.3233/jad-160227 CrossRefPubMedPubMedCentral

65.

Degerman Gunnarsson M, Ingelsson M, Blennow K, Basun H, Lannfelt L, Kilander L (2016) High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer’s disease. Alzheimers Res Ther 8:22. https://doi.org/10.1186/s13195-016-0191-0 CrossRefPubMedPubMedCentral

66.

Delgado-Alvarado M, Gago B, Gorostidi A, Jiménez-Urbieta H, Dacosta-Aguayo R, Navalpotro-Gómez I et al (2017) Tau/alpha-synuclein ratio and inflammatory proteins in Parkinson’s disease: an exploratory study. Mov Disord 32:1066–1073. https://doi.org/10.1002/mds.27001 CrossRefPubMed

67.

Desikan RS, Thompson WK, Holland D, Hess CP, Brewer JB, Zetterberg H et al (2013) Heart fatty acid binding protein and Aβ-associated Alzheimer’s neurodegeneration. Mol Neurodegener 8:39. https://doi.org/10.1186/1750-1326-8-39 CrossRefPubMedPubMedCentral

68.

Deters KD, Risacher SL, Kim S, Nho K, West JD, Blennow K et al (2017) Plasma tau association with brain atrophy in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 58:1245–1254. https://doi.org/10.3233/JAD-161114 CrossRefPubMedPubMedCentral

69.

Di Marco LY, Venneri A, Farkas E, Evans PC, Marzo A, Frangi AF (2015) Vascular dysfunction in the pathogenesis of Alzheimer’s disease—a review of endothelium-mediated mechanisms and ensuing vicious circles. Neurobiol Dis 82:593–606. https://doi.org/10.1016/j.nbd.2015.08.014 CrossRefPubMed

70.

Díez-Guerra FJ (2010) Neurogranin, a link between calcium/calmodulin and protein kinase C signaling in synaptic plasticity. IUBMB Life 62:597–606. https://doi.org/10.1002/iub.357 CrossRefPubMed

71.

Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A et al (2017) Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol 81:857–870. https://doi.org/10.1002/ana.24954 CrossRefPubMedPubMedCentral

72.

Doody RS, Thomas RG, Farlow M, Iwatsubo T, Vellas B, Joffe S et al (2014) Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 370:311–321. https://doi.org/10.1056/NEJMoa1312889 CrossRefPubMed

73.

Dorey A, Perret-Liaudet A, Tholance Y, Fourier A, Quadrio I (2015) Cerebrospinal fluid Aβ40 improves the interpretation of Aβ42 concentration for diagnosing Alzheimer’s disease. Front Neurol 6:247. https://doi.org/10.3389/fneur.2015.00247 CrossRefPubMedPubMedCentral

74.

Downes EC, Robson J, Grailly E, Abdel-All Z, Xuereb J, Brayne C et al (2008) Loss of synaptophysin and synaptosomal-associated protein 25-kDa (SNAP-25) in elderly down syndrome individuals. Neuropathol Appl Neurobiol 34:12–22. https://doi.org/10.1111/j.1365-2990.2007.00899.x CrossRefPubMed

75.

Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K et al (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13:614–629. https://doi.org/10.1016/s1474-4422(14)70090-0 CrossRefPubMed

76.

Engelborghs S, Niemantsverdriet E, Struyfs H, Blennow K, Brouns R, Comabella M et al (2017) Consensus guidelines for lumbar puncture in patients with neurological diseases. Alzheimers Dement (Amst) 8:111–126. https://doi.org/10.1016/j.dadm.2017.04.007 CrossRef

77.

European Medicines Agency, Committee for Medicinal Products for Human Use (2011) Qualification opinion of Alzheimer’s disease novel methodologies/biomarkers for the use of CSF amyloid beta 1-42 and t-tau signature and/or PET-amyloid imaging (positive/negative) as biomarkers for enrichment, for use in regulatory clinical trials in mild and moderate Alzheimer’s disease. http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2011/12/WC500118365.pdf

78.

European Medicines Agency, Committee for Medicinal Products for Human Use (2018) Guideline on the clinical investigation of medicines for the treatment of Alzheimer’s disease. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2018/02/WC500244609.pdf

79.

Ewers M, Cheng X, Zhong Z, Nural HF, Walsh C, Meindl T et al (2011) Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer’s disease. J Alzheimers Dis 25:373–381. https://doi.org/10.3233/jad-2011-091153 CrossRefPubMed

80.

Ewers M, Mattsson N, Minthon L, Molinuevo JL, Antonell A, Popp J et al (2015) CSF biomarkers for the differential diagnosis of Alzheimer’s disease: a large-scale international multicenter study. Alzheimers Dement 11:1306–1315. https://doi.org/10.1016/j.jalz.2014.12.006 CrossRefPubMed

81.

Ewers M, Zhong Z, Bürger K, Wallin A, Blennow K, Teipel SJ et al (2008) Increased CSF-BACE 1 activity is associated with ApoE-ε4 genotype in subjects with mild cognitive impairment and Alzheimer’s disease. Brain 131:1252–1258. https://doi.org/10.1093/brain/awn034 CrossRefPubMed

82.

Fagan AM, Mintun MA, Mach RH, Lee SY, Dence CS, Shah AR et al (2006) Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Aβ42 in humans. Ann Neurol 59:512–519. https://doi.org/10.1002/ana.20730 CrossRefPubMed

83.

Fagan AM, Mintun MA, Shah AR, Aldea P, Roe CM, Mach RH et al (2009) Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer’s disease. EMBO Mol Med 1:371–380. https://doi.org/10.1002/emmm.200900048 CrossRefPubMedPubMedCentral

84.

Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM (2007) Cerebrospinal fluid tau/β-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol 64:343–349. https://doi.org/10.1001/archneur.64.3.noc60123 CrossRefPubMed

85.

Fagan AM, Shaw LM, Xiong C, Vanderstichele H, Mintun MA, Trojanowski JQ et al (2011) Comparison of analytical platforms for cerebrospinal fluid measures of β-amyloid 1-42, total tau, and p-tau181 for identifying Alzheimer disease amyloid plaque pathology. Arch Neurol 68:1137–1144. https://doi.org/10.1001/archneurol.2011.105 CrossRefPubMedPubMedCentral

86.

Fairfoul G, McGuire LI, Pal S, Ironside JW, Neumann J, Christie S et al (2016) Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Transl Neurol 3:812–818. https://doi.org/10.1002/acn3.338 CrossRefPubMedPubMedCentral

87.

Fandos N, Pérez-Grijalba V, Pesini P, Olmos S, Bossa M, Villemagne VL et al (2017) Plasma amyloid β 42/40 ratios as biomarkers for amyloid β cerebral deposition in cognitively normal individuals. Alzheimers Dement (Amst) 8:179–187. https://doi.org/10.1016/j.dadm.2017.07.004 CrossRef

88.

Farlow M, Arnold SE, van Dyck CH, Aisen PS, Snider BJ, Porsteinsson AP et al (2012) Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement 8:261–271. https://doi.org/10.1016/j.jalz.2011.09.224 CrossRefPubMed

89.

Fath T, Eidenmuller J, Brandt R (2002) Tau-mediated cytotoxicity in a pseudohyperphosphorylation model of Alzheimer’s disease. J Neurosci 22:9733–9741CrossRefPubMedPubMedCentral

90.

Feneberg E, Steinacker P, Lehnert S, Schneider A, Walther P, Thal DR et al (2014) Limited role of free TDP-43 as a diagnostic tool in neurodegenerative diseases. Amyotroph Lateral Scler Frontotemporal Degener 15:351–356. https://doi.org/10.3109/21678421.2014.905606 CrossRefPubMed

91.

Ferreira D, Rivero-Santana A, Perestelo-Pérez L, Westman E, Wahlund LO, Sarría A et al (2014) Improving CSF biomarkers’ performance for predicting progression from mild cognitive impairment to Alzheimer’s disease by considering different confounding factors: a meta-analysis. Front Aging Neurosci 6:287. https://doi.org/10.3389/fnagi.2014.00287 CrossRefPubMedPubMedCentral

92.

Ferretti M, Lulita M, Cavedo E, Chiesa P, Schumacher Dimech A, Chadha Santuccione A et al (2018) Sex-specific phenotypes of Alzheimer’s disease: the gateway to precision neurology. Nat Rev Neurol 14:457–469. https://doi.org/10.1038/s41582-018-0032-9 CrossRefPubMed

93.

Finnema SJ, Nabulsi NB, Eid T, Detyniecki K, Lin SF, Chen MK et al (2016) Imaging synaptic density in the living human brain. Sci Transl Med 8:348ra396. https://doi.org/10.1126/scitranslmed.aaf6667 CrossRef

94.

Fleck D, van Bebber F, Colombo A, Galante C, Schwenk BM, Rabe L et al (2013) Dual cleavage of neuregulin 1 type III by BACE1 and ADAM17 liberates its EGF-like domain and allows paracrine signaling. J Neurosci 33:7856–7869. https://doi.org/10.1523/JNEUROSCI.3372-12.2013 CrossRefPubMedPubMedCentral

95.

Food and Drug Administration (2011) Guidance for industry—E16 biomarkers related to drug or biotechnology product development: context, structure, and format of qualification submissions. https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm267449.pdf

96.

Food and Drug Administration (2018) Early Alzheimer’s disease: developing drugs for treatment; draft guidance for industry. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM596728.pdf

97.

Foulds P, McAuley E, Gibbons L, Davidson Y, Pickering-Brown SM, Neary D et al (2008) TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer’s disease and frontotemporal lobar degeneration. Acta Neuropathol 116:141–146. https://doi.org/10.1007/s00401-008-0389-8 CrossRefPubMedPubMedCentral

98.

Fourier A, Portelius E, Zetterberg H, Blennow K, Quadrio I, Perret-Liaudet A (2015) Pre-analytical and analytical factors influencing Alzheimer’s disease cerebrospinal fluid biomarker variability. Clin Chim Acta 449:9–15. https://doi.org/10.1016/j.cca.2015.05.024 CrossRefPubMed

99.

Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, Mehta PD et al (2003) Biological markers for therapeutic trials in Alzheimer’s disease. Proceedings of the biological markers working group; NIA initiative on neuroimaging in Alzheimer’s disease. Neurobiol Aging 24:521–536

100.

Frisoni GB, Boccardi M, Barkhof F, Blennow K, Cappa S, Chiotis K et al (2017) Strategic roadmap for an early diagnosis of Alzheimer’s disease based on biomarkers. Lancet Neurol 16:661–676. https://doi.org/10.1016/S1474-4422(17)30159-X CrossRefPubMed

101.

Galimberti D, Schoonenboom N, Scheltens P, Fenoglio C, Bouwman F, Venturelli E et al (2006) Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol 63:538–543. https://doi.org/10.1001/archneur.63.4.538 CrossRefPubMed

102.

Galimberti D, Venturelli E, Fenoglio C, Lovati C, Guidi I, Scalabrini D et al (2007) IP-10 serum levels are not increased in mild cognitive impairment and Alzheimer’s disease. Eur J Neurol 14:e3–e4. https://doi.org/10.1111/j.1468-1331.2006.01637.x CrossRefPubMed

103.

Gendron TF, C9ORF72 Neurofilament Study Group, Daughrity LM, Heckman MG, Diehl NN, Wuu J et al (2017) Phosphorylated neurofilament heavy chain: a biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis. Ann Neurol 82:139–146. https://doi.org/10.1002/ana.24980

104.

Gervaise-Henry C, Watfa G, Albuisson E, Kolodziej A, Dousset B, Olivier JL et al (2017) Cerebrospinal fluid Aβeta42/Aβeta40 as a means to limiting tube- and storage-dependent pre-analytical variability in clinical setting. J Alzheimers Dis 57:437–445. https://doi.org/10.3233/jad-160865 CrossRefPubMed

105.

Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT et al (2003) Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 300:636–640. https://doi.org/10.1126/science.1082324 CrossRefPubMed

106.

Gispert JD, Monte GC, Suárez-Calvet M, Falcon C, Tucholka A, Rojas S et al (2017) The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer’s disease but not those of sTREM2. Alzheimers Dement (Amst) 6:50–59. https://doi.org/10.1016/j.dadm.2016.12.002 CrossRef

107.

Gispert JD, Suárez-Calvet M, Monté GC, Tucholka A, Falcon C, Rojas S et al (2016) Cerebrospinal fluid sTREM2 levels are associated with gray matter volume increases and reduced diffusivity in early Alzheimer’s disease. Alzheimers Dement 12:1259–1272. https://doi.org/10.1016/j.jalz.2016.06.005 CrossRefPubMed

108.

Glenner GG, Wong CW (1984) Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun 122:1131–1135CrossRefPubMed

109.

Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890CrossRefPubMed

110.

Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL et al (2016) Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer’s disease. FASEB J 30:4141–4148. https://doi.org/10.1096/fj.201600816R CrossRefPubMedPubMedCentral

111.

Goossens J, Vanmechelen E, Trojanowski JQ, Lee VM, Van Broeckhoven C, van der Zee J et al (2015) TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a systematic review of existing antibodies. Acta Neuropathol Commun 3:15. https://doi.org/10.1186/s40478-015-0195-1 CrossRefPubMedPubMedCentral

112.

Goozee K, Chatterjee P, James I, Shen K, Sohrabi HR, Asih PR et al (2018) Elevated plasma ferritin in elderly individuals with high neocortical amyloid-beta load. Mol Psychiatry 23:1807–1812. https://doi.org/10.1038/mp.2017.146 CrossRefPubMed

113.

Gravina SA, Ho L, Eckman CB, Long KE, Otvos L Jr, Younkin LH et al (1995) Amyloid beta protein (A beta) in Alzheimer’s disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43). J Biol Chem 270:7013–7016CrossRefPubMed

114.

Grimmer T, Riemenschneider M, Förstl H, Henriksen G, Klunk WE, Mathis CA et al (2009) Beta amyloid in Alzheimer’s disease: increased deposition in brain is reflected in reduced concentration in cerebrospinal fluid. Biol Psychiatry 65:927–934. https://doi.org/10.1016/j.biopsych.2009.01.027 CrossRefPubMedPubMedCentral

115.

Groblewska M, Muszynski P, Wojtulewska-Supron A, Kulczynska-Przybik A, Mroczko B (2015) The role of visinin-like protein-1 in the pathophysiology of Alzheimer’s disease. J Alzheimers Dis 47:17–32. https://doi.org/10.3233/jad-150060 CrossRefPubMed

116.

Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E et al (2013) TREM2 variants in Alzheimer’s disease. N Engl J Med 368:117–127. https://doi.org/10.1056/NEJMoa1211851 CrossRefPubMed

117.

Gunn AP, Masters CL, Cherny RA (2010) Pyroglutamate-Aβ: role in the natural history of Alzheimer’s disease. Int J Biochem Cell Biol 42:1915–1918. https://doi.org/10.1016/j.biocel.2010.08.015 CrossRefPubMed

118.

Guo JL, Lee VM (2014) Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med 20:130–138. https://doi.org/10.1038/nm.3457 CrossRefPubMedPubMedCentral

119.

Guo LH, Alexopoulos P, Perneczky R (2013) Heart-type fatty acid binding protein and vascular endothelial growth factor: cerebrospinal fluid biomarker candidates for Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 263:553–560. https://doi.org/10.1007/s00406-013-0405-4 CrossRefPubMed

120.

Guo R, Fan G, Zhang J, Wu C, Du Y, Ye H et al (2017) A 9-microRNA signature in serum serves as a noninvasive biomarker in early diagnosis of Alzheimer’s disease. J Alzheimers Dis 60:1365–1377. https://doi.org/10.3233/JAD-170343 CrossRefPubMed

121.

Hamilton RL (2000) Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol 10:378–384CrossRefPubMed

122.

Hampel H, Bürger K, Teipel SJ, Bokde AL, Zetterberg H, Blennow K (2008) Core candidate neurochemical and imaging biomarkers of Alzheimer’s disease. Alzheimers Dement 4:38–48. https://doi.org/10.1016/j.jalz.2007.08.006 CrossRefPubMed

123.

Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J et al (2010) Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov 9:560–574. https://doi.org/10.1038/nrd3115 CrossRefPubMed

124.

Hampel H, Lista S, Khachaturian ZS (2012) Development of biomarkers to chart all Alzheimer’s disease stages: the royal road to cutting the therapeutic Gordian Knot. Alzheimers Dement 8:312–336. https://doi.org/10.1016/j.jalz.2012.05.2116 CrossRefPubMed

125.

Hampel H, Lista S, Teipel SJ, Garaci F, Nisticó R, Blennow K et al (2014) Perspective on future role of biological markers in clinical therapy trials of Alzheimer’s disease: a long-range point of view beyond 2020. Biochem Pharmacol 88:426–449. https://doi.org/10.1016/j.bcp.2013.11.009 CrossRefPubMed

126.

Hampel H, O’Bryant SE, Castrillo JI, Ritchie C, Rojkova K, Broich K et al (2016) PRECISION MEDICINE—the Golden Gate for detection, treatment and prevention of Alzheimer’s disease. J Prev Alzheimers Dis 3:243–259. https://doi.org/10.14283/jpad.2016.112 CrossRefPubMedPubMedCentral

127.

Hampel H, O’Bryant SE, Durrleman S, Younesi E, Rojkova K, Escott-Price V et al (2017) A precision medicine initiative for Alzheimer’s disease: the road ahead to biomarker-guided integrative disease modeling. Climacteric 20:107–118. https://doi.org/10.1080/13697137.2017.1287866 CrossRefPubMed

128.

Hampel H, O’Bryant SE, Molinuevo JL, Zetterberg H, Masters CL, Lista S et al (2018) Blood-based biomarkers for Alzheimer’s disease: mapping the road to the clinic. Nat Rev Neurol 14:639–652. https://doi.org/10.1038/s41582-018-0079-7 CrossRefPubMedPubMedCentral

129.

Hampel H, Toschi N, Babiloni C, Baldacci F, Black KL, Bokde ALW et al (2018) Revolution of Alzheimer precision neurology. Passageway of systems biology and neurophysiology. J Alzheimers Dis 64(Suppl 1):S47–S105. https://doi.org/10.3233/JAD-179932 CrossRefPubMedPubMedCentral

130.

Hampel H, Vergallo A, Aguilar LF, Benda N, Broich K, Cuello AC et al (2018) Precision pharmacology for Alzheimer’s disease. Pharmacol Res 130:331–365. https://doi.org/10.1016/j.phrs.2018.02.014 CrossRefPubMedPubMedCentral

131.

Han J, Pluhackova K, Böckmann RA (2017) The multifaceted role of SNARE proteins in membrane fusion. Front Physiol 8:5. https://doi.org/10.3389/fphys.2017.00005 CrossRefPubMedPubMedCentral

132.

Hansson O, Hall S, Ohrfelt A, Zetterberg H, Blennow K, Minthon L et al (2014) Levels of cerebrospinal fluid α-synuclein oligomers are increased in Parkinson’s disease with dementia and dementia with Lewy bodies compared to Alzheimer’s disease. Alzheimers Res Ther 6:25. https://doi.org/10.1186/alzrt255 CrossRefPubMedPubMedCentral

133.

Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L (2006) Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5:228–234. https://doi.org/10.1016/S1474-4422(06)70355-6 CrossRefPubMed

134.

Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185CrossRefPubMed

135.

Hare D, Ayton S, Bush A, Lei P (2013) A delicate balance: iron metabolism and diseases of the brain. Front Aging Neurosci 5:34. https://doi.org/10.3389/fnagi.2013.00034 CrossRefPubMedPubMedCentral

136.

He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L et al (2018) Amyloid-β plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24:29–38. https://doi.org/10.1038/nm.4443 CrossRefPubMed

137.

Heinonen O, Soininen H, Sorvari H, Kosunen O, Paljärvi L, Koivisto E et al (1995) Loss of synaptophysin-like immunoreactivity in the hippocampal formation is an early phenomenon in Alzheimer’s disease. Neuroscience 64:375–384CrossRefPubMed

138.

Hellwig K, Kvartsberg H, Portelius E, Andreasson U, Oberstein TJ, Lewczuk P et al (2015) Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther 7:74. https://doi.org/10.1186/s13195-015-0161-y CrossRefPubMedPubMedCentral

139.

Henjum K, Almdahl IS, Årskog V, Minthon L, Hansson O, Fladby T et al (2016) Cerebrospinal fluid soluble TREM2 in aging and Alzheimer’s disease. Alzheimers Res Ther 8:17. https://doi.org/10.1186/s13195-016-0182-1 CrossRefPubMedPubMedCentral

140.

Henriksen K, O’Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A et al (2014) The future of blood-based biomarkers for Alzheimer’s disease. Alzheimers Dement 10:115–131. https://doi.org/10.1016/j.jalz.2013.01.013 CrossRefPubMed

141.

Heslegrave A, Heywood W, Paterson R, Magdalinou N, Svensson J, Johansson P et al (2016) Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease. Mol Neurodegener 11:3. https://doi.org/10.1186/s13024-016-0071-x CrossRefPubMedPubMedCentral

142.

Hesse R, Wahler A, Gummert P, Kirschmer S, Otto M, Tumani H et al (2016) Decreased IL-8 levels in CSF and serum of AD patients and negative correlation of MMSE and IL-1β. BMC Neurol 16:185. https://doi.org/10.1186/s12883-016-0707-z CrossRefPubMedPubMedCentral

143.

Hölttä M, Hansson O, Andreasson U, Hertze J, Minthon L, Nägga K et al (2013) Evaluating amyloid-β oligomers in cerebrospinal fluid as a biomarker for Alzheimer’s disease. PLoS One 8:e66381. https://doi.org/10.1371/journal.pone.0066381 CrossRefPubMedPubMedCentral

144.

Horrocks MH, Lee SF, Gandhi S, Magdalinou NK, Chen SW, Devine MJ et al (2016) Single-molecule imaging of individual amyloid protein aggregates in human biofluids. ACS Chem Neurosci 7:399–406. https://doi.org/10.1021/acschemneuro.5b00324 CrossRefPubMed

145.

Hu N, Tan MS, Yu JT, Sun L, Tan L, Wang YL et al (2014) Increased expression of TREM2 in peripheral blood of Alzheimer’s disease patients. J Alzheimers Dis 38:497–501. https://doi.org/10.3233/jad-130854 CrossRefPubMed

146.

Hu WT, Chen-Plotkin A, Arnold SE, Grossman M, Clark CM, Shaw LM et al (2010) Novel CSF biomarkers for Alzheimer’s disease and mild cognitive impairment. Acta Neuropathol 119:669–678. https://doi.org/10.1007/s00401-010-0667-0 CrossRefPubMedPubMedCentral

147.

Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC et al (1999) The A beta peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38:7609–7616. https://doi.org/10.1021/bi990438f CrossRefPubMed

148.

Hulstaert F, Blennow K, Ivanoiu A, Schoonderwaldt HC, Riemenschneider M, De Deyn PP et al (1999) Improved discrimination of AD patients using β-amyloid(1-42) and tau levels in CSF. Neurology 52:1555–1562CrossRefPubMed

149.

Huynh RA, Mohan C (2017) Alzheimer’s disease: biomarkers in the genome, blood, and cerebrospinal fluid. Front Neurol 8:102. https://doi.org/10.3389/fneur.2017.00102 CrossRefPubMedPubMedCentral

150.

Inekci D, Henriksen K, Linemann T, Karsdal MA, Habib A, Bisgaard C et al (2015) Serum fragments of tau for the differential diagnosis of Alzheimer’s disease. Curr Alzheimer Res 12:829–836CrossRefPubMed

151.

Ingelsson M (2016) Alpha-synuclein oligomers-neurotoxic molecules in Parkinson’s disease and other Lewy body disorders. Front Neurosci 10:408. https://doi.org/10.3389/fnins.2016.00408 CrossRefPubMedPubMedCentral

152.

Irwin DJ (2016) Tauopathies as clinicopathological entities. Parkinsonism Relat Disord 22(Suppl 1):S29–S33. https://doi.org/10.1016/j.parkreldis.2015.09.020 CrossRefPubMed

153.

Isaac M, Vamvakas S, Abadie E, Jonsson B, Gispen C, Pani L (2011) Qualification opinion of novel methodologies in the predementia stage of Alzheimer’s disease: cerebro-spinal-fluid related biomarkers for drugs affecting amyloid burden—regulatory considerations by European Medicines Agency focusing in improving benefit/risk in regulatory trials. Eur Neuropsychopharmacol 21:781–788. https://doi.org/10.1016/j.euroneuro.2011.08.003 CrossRefPubMed

154.

Iturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-Pérez JM, Evans AC, Alzheimer’s Disease Neuroimaging Initiative (2016) Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nat Commun 7:11934. https://doi.org/10.1038/ncomms11934 CrossRefPubMedPubMedCentral

155.

Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y (1994) Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: evidence that an initially deposited species is Aβ42(43). Neuron 13:45–53CrossRefPubMed

156.

Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS et al (2013) Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12:207–216. https://doi.org/10.1016/S1474-4422(12)70291-0 CrossRefPubMedPubMedCentral

157.

Jackson K, Barisone GA, Diaz E, Jin LW, DeCarli C, Despa F (2013) Amylin deposition in the brain: a second amyloid in Alzheimer disease? Ann Neurol 74:517–526. https://doi.org/10.1002/ana.23956 CrossRefPubMed

158.

Jagust WJ, Landau SM, Shaw LM, Trojanowski JQ, Koeppe RA, Reiman EM et al (2009) Relationships between biomarkers in aging and dementia. Neurology 73:1193–1199. https://doi.org/10.1212/WNL.0b013e3181bc010c CrossRefPubMedPubMedCentral

159.

James BD, Wilson RS, Boyle PA, Trojanowski JQ, Bennett DA, Schneider JA (2016) TDP-43 stage, mixed pathologies, and clinical Alzheimer’s-type dementia. Brain 139:2983–2993. https://doi.org/10.1093/brain/aww224 CrossRefPubMedPubMedCentral

160.

Janelidze S, Stomrud E, Palmqvist S, Zetterberg H, van Westen D, Jeromin A et al (2016) Plasma β-amyloid in Alzheimer’s disease and vascular disease. Sci Rep 6:26801. https://doi.org/10.1038/srep26801 CrossRefPubMedPubMedCentral

161.

Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O et al (2016) CSF Aβ42/Aβ40 and Aβ42/Aβ38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol 3:154–165. https://doi.org/10.1002/acn3.274 CrossRefPubMedPubMedCentral

162.

Jay TR, von Saucken VE, Landreth GE (2017) TREM2 in neurodegenerative diseases. Mol Neurodegener 12:56. https://doi.org/10.1186/s13024-017-0197-5 CrossRefPubMedPubMedCentral

163.

Josephs KA, Whitwell JL, Knopman DS, Hu WT, Stroh DA, Baker M et al (2008) Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 70:1850–1857. https://doi.org/10.1212/01.wnl.0000304041.09418.b1 CrossRefPubMed

164.

Jucker M, Walker LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501:45–51. https://doi.org/10.1038/nature12481 CrossRefPubMedPubMedCentral

165.

Junttila A, Kuvaja M, Hartikainen P, Siloaho M, Helisalmi S, Moilanen V et al (2016) Cerebrospinal fluid TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis patients with and without the C9ORF72 hexanucleotide expansion. Dement Geriatr Cogn Dis Extra 6:142–149. https://doi.org/10.1159/000444788 CrossRefPubMedPubMedCentral

166.

Kakuda N, Miyasaka T, Iwasaki N, Nirasawa T, Wada-Kakuda S, Takahashi-Fujigasaki J et al (2017) Distinct deposition of amyloid-beta species in brains with Alzheimer’s disease pathology visualized with MALDI imaging mass spectrometry. Acta Neuropathol Commun 5:73. https://doi.org/10.1186/s40478-017-0477-x CrossRefPubMedPubMedCentral

167.

Kamat PK, Kalani A, Rai S, Swarnkar S, Tota S, Nath C et al (2016) Mechanism of oxidative stress and synapse dysfunction in the pathogenesis of Alzheimer’s disease: understanding the therapeutics strategies. Mol Neurobiol 53:648–661. https://doi.org/10.1007/s12035-014-9053-6 CrossRefPubMed

168.

Kang JH, Irwin DJ, Chen-Plotkin AS, Siderowf A, Caspell C, Coffey CS et al (2013) Association of cerebrospinal fluid β-amyloid 1-42, t-tau, p-tau181, and α-synuclein levels with clinical features of drug-naive patients with early Parkinson disease. JAMA Neurol 70:1277–1287. https://doi.org/10.1001/jamaneurol.2013.3861 CrossRefPubMedPubMedCentral

169.

Kang JH, Mollenhauer B, Coffey CS, Toledo JB, Weintraub D, Galasko DR et al (2016) CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study. Acta Neuropathol 131:935–949. https://doi.org/10.1007/s00401-016-1552-2 CrossRefPubMedPubMedCentral

170.

Kapaki E, Paraskevas GP, Emmanouilidou E, Vekrellis K (2013) The diagnostic value of CSF α-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer’s disease. PLoS One 8:e81654. https://doi.org/10.1371/journal.pone.0081654 CrossRefPubMedPubMedCentral

171.

Kasai T, Tokuda T, Ishii R, Ishigami N, Tsuboi Y, Nakagawa M et al (2014) Increased α-synuclein levels in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. J Neurol 261:1203–1209. https://doi.org/10.1007/s00415-014-7334-7 CrossRefPubMed

172.

Kasuga K, Tokutake T, Ishikawa A, Uchiyama T, Tokuda T, Onodera O et al (2010) Differential levels of α-synuclein, β-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 81:608–610. https://doi.org/10.1136/jnnp.2009.197483 CrossRefPubMed

173.

Kennedy ME, Stamford AW, Chen X, Cox K, Cumming JN, Dockendorf MF et al (2016) The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients. Sci Transl Med 8:363ra150. https://doi.org/10.1126/scitranslmed.aad9704 CrossRefPubMed

174.

Kerchner G, Ayalon G, Blendstrup M, Brunstein F, Chandra P, Datwani A et al (2017) Targeting tau with RO7105705: Phase I results and design of a Phase II study in prodromal-to-mild AD. Abstract presented at the 10th Clinical Trials on Alzheimer’s Disease (CTAD). Boston (1–4 November 2017)

175.

Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P et al (2015) Neurogranin as a cerebrospinal fluid biomarker for synaptic loss in symptomatic Alzheimer disease. JAMA Neurol 72:1275–1280. https://doi.org/10.1001/jamaneurol.2015.1867 CrossRefPubMedPubMedCentral

176.

Kester MI, Teunissen CE, Sutphen C, Herries EM, Ladenson JH, Xiong C et al (2015) Cerebrospinal fluid VILIP-1 and YKL-40, candidate biomarkers to diagnose, predict and monitor Alzheimer’s disease in a memory clinic cohort. Alzheimers Res Ther 7:59. https://doi.org/10.1186/s13195-015-0142-1 CrossRefPubMedPubMedCentral

177.

Khan SS, Bloom GS (2016) Tau: the center of a signaling nexus in Alzheimer’s disease. Front Neurosci 10:31. https://doi.org/10.3389/fnins.2016.00031 CrossRefPubMedPubMedCentral

178.

Kim D, Kim YS, Shin DW, Park CS, Kang JH (2016) Harnessing cerebrospinal fluid biomarkers in clinical trials for treating Alzheimer’s and Parkinson’s diseases: potential and challenges. J Clin Neurol 12:381–392. https://doi.org/10.3988/jcn.2016.12.4.381 CrossRefPubMedPubMedCentral

179.

Kim HJ, Park KW, Kim TE, Im JY, Shin HS, Kim S et al (2015) Elevation of the plasma Aβ40/Aβ42 ratio as a diagnostic marker of sporadic early-onset Alzheimer’s disease. J Alzheimers Dis 48:1043–1050. https://doi.org/10.3233/JAD-143018 CrossRefPubMed

180.

Kim J, Onstead L, Randle S, Price R, Smithson L, Zwizinski C et al (2007) Aβ40 inhibits amyloid deposition in vivo. J Neurosci 27:627–633. https://doi.org/10.1523/jneurosci.4849-06.2007 CrossRefPubMedPubMedCentral

181.

Kim WS, Kågedal K, Halliday GM (2014) Alpha-synuclein biology in Lewy body diseases. Alzheimers Res Ther 6:73. https://doi.org/10.1186/s13195-014-0073-2 CrossRefPubMedPubMedCentral

182.

Komori M, Kosa P, Stein J, Zhao V, Blake A, Cherup J et al (2017) Pharmacodynamic effects of daclizumab in the intrathecal compartment. Ann Clin Transl Neurol 4:478–490. https://doi.org/10.1002/acn3.427 CrossRefPubMedPubMedCentral

183.

Korff A, Liu C, Ginghina C, Shi M, Zhang J, Initiative Alzheimer’s Disease Neuroimaging (2013) α-Synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis 36:679–688. https://doi.org/10.3233/jad-130458 CrossRefPubMedPubMedCentral

184.

Kuhle J, Nourbakhsh B, Grant D, Morant S, Barro C, Yaldizli O et al (2017) Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology 88:826–831. https://doi.org/10.1212/wnl.0000000000003653 CrossRefPubMedPubMedCentral

185.

Kuhlmann J, Andreasson U, Pannee J, Bjerke M, Portelius E, Leinenbach A et al (2017) CSF Abeta1-42—an excellent but complicated Alzheimer’s biomarker—a route to standardisation. Clin Chim Acta 467:27–33. https://doi.org/10.1016/j.cca.2016.05.014 CrossRefPubMed

186.

Kuhn PH, Koroniak K, Hogl S, Colombo A, Zeitschel U, Willem M et al (2012) Secretome protein enrichment identifies physiological BACE1 protease substrates in neurons. EMBO J 31:3157–3168. https://doi.org/10.1038/emboj.2012.173 CrossRefPubMedPubMedCentral

187.

Kuiperij HB, Versleijen AA, Beenes M, Verwey NA, Benussi L, Paterlini A et al (2017) Tau rather than TDP-43 proteins are potential cerebrospinal fluid biomarkers for frontotemporal lobar degeneration subtypes: a pilot study. J Alzheimers Dis 55:585–595. https://doi.org/10.3233/jad-160386 CrossRefPubMed

188.

Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M et al (2010) Neurotoxicity of Alzheimer’s disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio. EMBO J 29:3408–3420. https://doi.org/10.1038/emboj.2010.211 CrossRefPubMedPubMedCentral

189.

Kvartsberg H, Duits FH, Ingelsson M, Andreasen N, Öhrfelt A, Andersson K et al (2015) Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer’s disease. Alzheimers Dement 11:1180–1190. https://doi.org/10.1016/j.jalz.2014.10.009 CrossRefPubMed

190.

Kvartsberg H, Portelius E, Andreasson U, Brinkmalm G, Hellwig K, Lelental N et al (2015) Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer’s disease patients and healthy controls. Alzheimers Res Ther 7:40. https://doi.org/10.1186/s13195-015-0124-3 CrossRefPubMedPubMedCentral

191.

Lai KSP, Liu CS, Rau A, Lanctot KL, Kohler CA, Pakosh M et al (2017) Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies. J Neurol Neurosurg Psychiatry 88:876–882. https://doi.org/10.1136/jnnp-2017-316201 CrossRefPubMed

192.

Laterza OF, Modur VR, Crimmins DL, Olander JV, Landt Y, Lee JM et al (2006) Identification of novel brain biomarkers. Clin Chem 52:1713–1721. https://doi.org/10.1373/clinchem.2006.070912 CrossRefPubMed

193.

Lauridsen C, Sando SB, Moller I, Berge G, Pomary PK, Grontvedt GR et al (2017) Cerebrospinal fluid Abeta43 Is reduced in early-onset compared to late-onset Alzheimer’s Disease, but has similar diagnostic accuracy to Abeta42. Front Aging Neurosci 9:210. https://doi.org/10.3389/fnagi.2017.00210 CrossRefPubMedPubMedCentral

194.

Lee JM, Blennow K, Andreasen N, Laterza O, Modur V, Olander J et al (2008) The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clin Chem 54:1617–1623. https://doi.org/10.1373/clinchem.2008.104497 CrossRefPubMedPubMedCentral

195.

Lee PH, Lee G, Park HJ, Bang OY, Joo IS, Huh K (2006) The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy. J Neural Transm (Vienna) 113:1435–1439. https://doi.org/10.1007/s00702-005-0427-9 CrossRef

196.

Lee VM, Balin BJ, Otvos L Jr, Trojanowski JQ (1991) A68: a major subunit of paired helical filaments and derivatized forms of normal tau. Science 251:675–678CrossRefPubMed

197.

Lee VM, Trojanowski JQ (2001) Transgenic mouse models of tauopathies: prospects for animal models of Pick’s disease. Neurology 56:S26–S30CrossRefPubMed

198.

Leitão MJ, Baldeiras I, Herukka SK, Pikkarainen M, Leinonen V, Simonsen AH et al (2015) Chasing the effects of pre-analytical confounders—a multicenter study on CSF-AD biomarkers. Front Neurol 6:153. https://doi.org/10.3389/fneur.2015.00153 CrossRefPubMedPubMedCentral

199.

Lemstra AW, de Beer MH, Teunissen CE, Schreuder C, Scheltens P, van der Flier WM et al (2017) Concomitant AD pathology affects clinical manifestation and survival in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 88:113–118. https://doi.org/10.1136/jnnp-2016-313775 CrossRefPubMed

200.

Leschik J, Welzel A, Weissmann C, Eckert A, Brandt R (2007) Inverse and distinct modulation of tau-dependent neurodegeneration by presenilin 1 and amyloid-β in cultured cortical neurons: evidence that tau phosphorylation is the limiting factor in amyloid-β-induced cell death. J Neurochem 101:1303–1315. https://doi.org/10.1111/j.1471-4159.2006.04435.x CrossRefPubMed

201.

Leung YY, Toledo JB, Nefedov A, Polikar R, Raghavan N, Xie SX et al (2015) Identifying amyloid pathology-related cerebrospinal fluid biomarkers for Alzheimer’s disease in a multicohort study. Alzheimers Dement (Amst) 1:339–348. https://doi.org/10.1016/j.dadm.2015.06.008 CrossRef

202.

Leuzy A, Chiotis K, Hasselbalch SG, Rinne JO, de Mendonça A, Otto M et al (2016) Pittsburgh compound B imaging and cerebrospinal fluid amyloid-β in a multicentre European memory clinic study. Brain 139:2540–2553. https://doi.org/10.1093/brain/aww160 CrossRefPubMedPubMedCentral

203.

Leverenz JB, Fishel MA, Peskind ER, Montine TJ, Nochlin D, Steinbart E et al (2006) Lewy body pathology in familial Alzheimer disease: evidence for disease- and mutation-specific pathologic phenotype. Arch Neurol 63:370–376. https://doi.org/10.1001/archneur.63.3.370 CrossRefPubMedPubMedCentral

204.

Lewczuk P, Lelental N, Lachmann I, Holzer M, Flach K, Brandner S et al (2017) Non-phosphorylated tau as a potential biomarker of Alzheimer’s disease: analytical and diagnostic characterization. J Alzheimers Dis 55:159–170. https://doi.org/10.3233/JAD-160448 CrossRefPubMed

205.

Lewczuk P, Matzen A, Blennow K, Parnetti L, Molinuevo JL, Eusebi P et al (2017) Cerebrospinal fluid Aβ42/40 corresponds better than Aβ42 to amyloid PET in Alzheimer’s disease. J Alzheimers Dis 55:813–822. https://doi.org/10.3233/jad-160722 CrossRefPubMed

206.

Lewczuk P, Riederer P, O’Bryant SE, Verbeek MM, Dubois B, Visser PJ et al (2017) Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: an update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry. World J Biol Psychiatry. https://doi.org/10.1080/15622975.2017.1375556

207.

Lewis KA, Su Y, Jou O, Ritchie C, Foong C, Hynan LS et al (2010) Abnormal neurites containing C-terminally truncated alpha-synuclein are present in Alzheimer’s disease without conventional Lewy body pathology. Am J Pathol 177:3037–3050. https://doi.org/10.2353/ajpath.2010.100552 CrossRefPubMedPubMedCentral

208.

Leyhe T, Andreasen N, Simeoni M, Reich A, von Arnim CA, Tong X et al (2014) Modulation of beta-amyloid by a single dose of GSK933776 in patients with mild Alzheimer’s disease: a phase I study. Alzheimers Res Ther 6:19. https://doi.org/10.1186/alzrt249 CrossRefPubMedPubMedCentral

209.

Li G, Sokal I, Quinn JF, Leverenz JB, Brodey M, Schellenberg GD et al (2007) CSF tau/Aβ42 ratio for increased risk of mild cognitive impairment: a follow-up study. Neurology 69:631–639. https://doi.org/10.1212/01.wnl.0000267428.62582.aa CrossRefPubMed

210.

Li X, Lei P, Tuo Q, Ayton S, Li QX, Moon S et al (2015) Enduring elevations of hippocampal amyloid precursor protein and iron are features of β-amyloid toxicity and are mediated by tau. Neurotherapeutics 12:862–873. https://doi.org/10.1007/s13311-015-0378-2 CrossRefPubMedPubMedCentral

211.

Libreros S, Iragavarapu-Charyulu V (2015) YKL-40/CHI3L1 drives inflammation on the road of tumor progression. J Leukoc Biol 98:931–936. https://doi.org/10.1189/jlb.3VMR0415-142R CrossRefPubMedPubMedCentral

212.

Lin CH, Yang SY, Horng HE, Yang CC, Chieh JJ, Chen HH et al (2017) Plasma α-synuclein predicts cognitive decline in Parkinson’s disease. J Neurol Neurosurg Psychiatry 88:818–824. https://doi.org/10.1136/jnnp-2016-314857 CrossRefPubMed

213.

Lippa CF, Schmidt ML, Lee VM, Trojanowski JQ (1999) Antibodies to alpha-synuclein detect Lewy bodies in many Down’s syndrome brains with Alzheimer’s disease. Ann Neurol 45:353–357CrossRefPubMed

214.

Lista S, Emanuele E (2011) Role of amyloid beta1-42 and neuroimaging biomarkers in Alzheimer’s disease. Biomark Med 5:411–413. https://doi.org/10.2217/bmm.11.50 CrossRefPubMed

215.

Lista S, Faltraco F, Hampel H (2013) Biological and methodical challenges of blood-based proteomics in the field of neurological research. Prog Neurobiol 101–102:18–34. https://doi.org/10.1016/j.pneurobio.2012.06.006 CrossRefPubMed

216.

Lista S, Faltraco F, Prvulovic D, Hampel H (2013) Blood and plasma-based proteomic biomarker research in Alzheimer’s disease. Prog Neurobiol 101–102:1–17. https://doi.org/10.1016/j.pneurobio.2012.06.007 CrossRefPubMed

217.

Lista S, Garaci FG, Ewers M, Teipel S, Zetterberg H, Blennow K et al (2014) CSF Abeta1-42 combined with neuroimaging biomarkers in the early detection, diagnosis and prediction of Alzheimer’s disease. Alzheimers Dement 10:381–392. https://doi.org/10.1016/j.jalz.2013.04.506 CrossRefPubMed

218.

Lista S, Hampel H (2017) Synaptic degeneration and neurogranin in the pathophysiology of Alzheimer’s disease. Expert Rev Neurother 17:47–57. https://doi.org/10.1080/14737175.2016.1204234 CrossRefPubMed

219.

Lista S, Khachaturian ZS, Rujescu D, Garaci F, Dubois B, Hampel H (2016) Application of systems theory in longitudinal studies on the origin and progression of Alzheimer’s disease. Methods Mol Biol 1303:49–67. https://doi.org/10.1007/978-1-4939-2627-5_2 CrossRefPubMed

220.

Lista S, Toschi N, Baldacci F, Zetterberg H, Blennow K, Kilimann I et al (2017) Diagnostic accuracy of CSF neurofilament light chain protein in the biomarker-guided classification system for Alzheimer’s disease. Neurochem Int 108:355–360. https://doi.org/10.1016/j.neuint.2017.05.010 CrossRefPubMed

221.

Lista S, Toschi N, Baldacci F, Zetterberg H, Blennow K, Kilimann I et al (2017) Cerebrospinal fluid neurogranin as a biomarker of neurodegenerative diseases: a cross-sectional study. J Alzheimers Dis 59:1327–1334. https://doi.org/10.3233/jad-170368 CrossRefPubMed

222.

Lista S, Zetterberg H, O’Bryant SE, Blennow K, Hampel H (2017) Evolving relevance of neuroproteomics in Alzheimer’s disease. Methods Mol Biol 1598:101–115. https://doi.org/10.1007/978-1-4939-6952-4_5 CrossRefPubMed

223.

Liu M, Guo S, Hibbert JM, Jain V, Singh N, Wilson NO et al (2011) CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev 22:121–130. https://doi.org/10.1016/j.cytogfr.2011.06.001 CrossRefPubMedPubMedCentral

224.

Ljungqvist J, Zetterberg H, Mitsis M, Blennow K, Skoglund T (2017) Serum neurofilament light protein as a marker for diffuse axonal injury: results from a case series study. J Neurotrauma 34:1124–1127. https://doi.org/10.1089/neu.2016.4496 CrossRefPubMed

225.

Llorens F, Kruse N, Karch A, Schmitz M, Zafar S, Gotzmann N et al (2017) Validation of α-synuclein as a CSF biomarker for sporadic Creutzfeldt-Jakob disease. Mol Neurobiol 55:2249–2257. https://doi.org/10.1007/s12035-017-0479-5 CrossRefPubMedPubMedCentral

226.

Loeffler DA, Connor JR, Juneau PL, Snyder BS, Kanaley L, DeMaggio AJ et al (1995) Transferrin and iron in normal, Alzheimer’s disease, and Parkinson’s disease brain regions. J Neurochem 65:710–724CrossRefPubMed

227.

Lövheim H, Elgh F, Johansson A, Zetterberg H, Blennow K, Hallmans G et al (2017) Plasma concentrations of free amyloid β cannot predict the development of Alzheimer’s disease. Alzheimers Dement 13:778–782. https://doi.org/10.1016/j.jalz.2016.12.004 CrossRefPubMed

228.

Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N et al (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84:2247–2257. https://doi.org/10.1212/WNL.0000000000001642 CrossRefPubMedPubMedCentral

229.

Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ et al (2012) Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338:949–953. https://doi.org/10.1126/science.1227157 CrossRefPubMedPubMedCentral

230.

Luo X, Hou L, Shi H, Zhong X, Zhang Y, Zheng D et al (2013) CSF levels of the neuronal injury biomarker visinin-like protein-1 in Alzheimer’s disease and dementia with Lewy bodies. J Neurochem 127:681–690. https://doi.org/10.1111/jnc.12331 CrossRefPubMed

231.

Lycke JN, Karlsson JE, Andersen O, Rosengren LE (1998) Neurofilament protein in cerebrospinal fluid: a potential marker of activity in multiple sclerosis. J Neurol Neurosurg Psychiatry 64:402–404CrossRefPubMedPubMedCentral

232.

Majbour NK, Chiasserini D, Vaikath NN, Eusebi P, Tokuda T, van de Berg W et al (2017) Increased levels of CSF total but not oligomeric or phosphorylated forms of alpha-synuclein in patients diagnosed with probable Alzheimer’s disease. Sci Rep 7:40263. https://doi.org/10.1038/srep40263 CrossRefPubMedPubMedCentral

233.

Majbour NK, Vaikath NN, van Dijk KD, Ardah MT, Varghese S, Vesterager LB et al (2016) Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease. Mol Neurodegener 11:7. https://doi.org/10.1186/s13024-016-0072-9 CrossRefPubMedPubMedCentral

234.

Marsh SE, Blurton-Jones M (2012) Examining the mechanisms that link β-amyloid and α-synuclein pathologies. Alzheimers Res Ther 4:11. https://doi.org/10.1186/alzrt109 CrossRefPubMedPubMedCentral

235.

Masliah E, Hansen L, Albright T, Mallory M, Terry RD (1991) Immunoelectron microscopic study of synaptic pathology in Alzheimer’s disease. Acta Neuropathol 81:428–433CrossRefPubMed

236.

Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW Jr et al (2001) Altered expression of synaptic proteins occurs early during progression of Alzheimer’s disease. Neurology 56:127–129CrossRefPubMed

237.

Masliah E, Terry RD, Alford M, DeTeresa R, Hansen LA (1991) Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer’s disease. Am J Pathol 138:235–246PubMedPubMedCentral

238.

Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL (2015) Alzheimer’s disease. Nat Rev Dis Primers 1:15056. https://doi.org/10.1038/nrdp.2015.56 CrossRefPubMed

239.

Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82:4245–4249CrossRefPubMedPubMedCentral

240.

Mattsson N, Andreasson U, Zetterberg H, Blennow K, Alzheimer’s Disease Neuroimaging Initiative (2017) Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol 74:557–566. https://doi.org/10.1001/jamaneurol.2016.6117 CrossRefPubMedPubMedCentral

241.

Mattsson N, Carrillo MC, Dean RA, Devous MD Sr, Nikolcheva T, Pesini P et al (2015) Revolutionizing Alzheimer’s disease and clinical trials through biomarkers. Alzheimers Dement (Amst) 1:412–419. https://doi.org/10.1016/j.dadm.2015.09.001 CrossRef

242.

Mattsson N, Insel PS, Palmqvist S, Portelius E, Zetterberg H, Weiner M et al (2016) Cerebrospinal fluid tau, neurogranin, and neurofilament light in Alzheimer’s disease. EMBO Mol Med 8:1184–1196. https://doi.org/10.15252/emmm.201606540 CrossRefPubMedPubMedCentral

243.

Mattsson N, Insel PS, Palmqvist S, Stomrud E, van Westen D, Minthon L et al (2016) Increased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis. Nat Commun 7:10918. https://doi.org/10.1038/ncomms10918 CrossRefPubMedPubMedCentral

244.

Mattsson N, Tabatabaei S, Johansson P, Hansson O, Andreasson U, Månsson JE et al (2011) Cerebrospinal fluid microglial markers in Alzheimer’s disease: elevated chitotriosidase activity but lack of diagnostic utility. Neuromol Med 13:151–159. https://doi.org/10.1007/s12017-011-8147-9 CrossRef

245.

Mattsson N, Zetterberg H, Janelidze S, Insel PS, Andreasson U, Stomrud E et al (2016) Plasma tau in Alzheimer disease. Neurology 87:1827–1835. https://doi.org/10.1212/WNL.0000000000003246 CrossRefPubMedPubMedCentral

246.

McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C et al (2005) Aβ42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47:191–199. https://doi.org/10.1016/j.neuron.2005.06.030 CrossRefPubMedPubMedCentral

247.

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH et al (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269. https://doi.org/10.1016/j.jalz.2011.03.005 CrossRefPubMedPubMedCentral

248.

Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM (2000) Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease. Arch Neurol 57:100–105CrossRefPubMed

249.

Mellergård J, Tisell A, Blystad I, Grönqvist A, Blennow K, Olsson B et al (2017) Cerebrospinal fluid levels of neurofilament and tau correlate with brain atrophy in natalizumab-treated multiple sclerosis. Eur J Neurol 24:112–121. https://doi.org/10.1111/ene.13162 CrossRefPubMed

250.

Meredith JE Jr, Sankaranarayanan S, Guss V, Lanzetti AJ, Berisha F, Neely RJ et al (2013) Characterization of novel CSF tau and ptau biomarkers for Alzheimer’s disease. PLoS One 8:e76523. https://doi.org/10.1371/journal.pone.0076523 CrossRefPubMed

251.

Mielke MM, Hagen CE, Wennberg AMV, Airey DC, Savica R, Knopman DS et al (2017) Association of plasma total tau level with cognitive decline and risk of mild cognitive impairment or dementia in the Mayo Clinic Study on Aging. JAMA Neurol 74:1073–1080. https://doi.org/10.1001/jamaneurol.2017.1359 CrossRefPubMedPubMedCentral

252.

Mohorko N, Bresjanac M (2008) Tau protein and human tauopathies: an overview. Zdrav Vestn 77:II-35-41

253.

Mollenhauer B, Cullen V, Kahn I, Krastins B, Outeiro TF, Pepivani I et al (2008) Direct quantification of CSF α-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Exp Neurol 213:315–325. https://doi.org/10.1016/j.expneurol.2008.06.004 CrossRefPubMed

254.

Mollenhauer B, Steinacker P, Bahn E, Bibl M, Brechlin P, Schlossmacher MG et al (2007) Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: marker candidates for dementia with Lewy bodies. Neurodegener Dis 4:366–375. https://doi.org/10.1159/000105157 CrossRefPubMed

255.

Mori Y, Yoshino Y, Ochi S, Yamazaki K, Kawabe K, Abe M et al (2015) TREM2 mRNA expression in leukocytes is increased in Alzheimer’s disease and schizophrenia. PLoS One 10:e0136835. https://doi.org/10.1371/journal.pone.0136835 CrossRefPubMedPubMedCentral

256.

Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D et al (1995) Reduction of beta-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer’s disease. Ann Neurol 38:643–648. https://doi.org/10.1002/ana.410380413 CrossRefPubMed

257.

Mroczko B, Groblewska M, Zboch M, Muszynski P, Zajkowska A, Borawska R et al (2015) Evaluation of visinin-like protein 1 concentrations in the cerebrospinal fluid of patients with mild cognitive impairment as a dynamic biomarker of Alzheimer’s disease. J Alzheimers Dis 43:1031–1037. https://doi.org/10.3233/jad-141050 CrossRefPubMed

258.

Mulder SD, van der Flier WM, Verheijen JH, Mulder C, Scheltens P, Blankenstein MA et al (2010) BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology. J Alzheimers Dis 20:253–260. https://doi.org/10.3233/jad-2010-1367 CrossRefPubMed

259.

Mulugeta E, Londos E, Ballard C, Alves G, Zetterberg H, Blennow K et al (2011) CSF amyloid β38 as a novel diagnostic marker for dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 82:160–164. https://doi.org/10.1136/jnnp.2009.199398 CrossRefPubMed

260.

Naj AC, Schellenberg GD, Alzheimer’s Disease Genetics Consortium (2017) Genomic variants, genes, and pathways of Alzheimer’s disease: an overview. Am J Med Genet B Neuropsychiatr Genet 174:5–26. https://doi.org/10.1002/ajmg.b.32499

261.

Nakamura A, Kaneko N, Villemagne VL, Kato T, Doecke J, Doré V et al (2018) High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature 554:249–254. https://doi.org/10.1038/nature25456 CrossRefPubMed

262.

Nath S, Koziarz A, Badhiwala JH, Alhazzani W, Jaeschke R, Sharma S et al (2017) Atraumatic versus conventional lumbar puncture needles: a systematic review and meta-analysis. Lancet 391:1197–1204. https://doi.org/10.1016/S0140-6736(17)32451-0 CrossRefPubMed

263.

Nelson PT, Alafuzoff I, Bigio EH, Bouras C, Braak H, Cairns NJ et al (2012) Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J Neuropathol Exp Neurol 71:362–381. https://doi.org/10.1097/NEN.0b013e31825018f7 CrossRefPubMed

264.

Neumann K, Farías G, Slachevsky A, Perez P, Maccioni RB (2011) Human platelets tau: a potential peripheral marker for Alzheimer’s disease. J Alzheimers Dis 25:103–109. https://doi.org/10.3233/JAD-2011-101641 CrossRefPubMed

265.

Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT et al (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314:130–133. https://doi.org/10.1126/science.1134108 CrossRefPubMed

266.

Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, Malmeström C et al (2017) Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis. J Neurochem 141:296–304. https://doi.org/10.1111/jnc.13881 CrossRefPubMed

267.

Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, Malmeström C et al (2017) Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis. Mult Scler 23:62–71. https://doi.org/10.1177/1352458516639384 CrossRefPubMed

268.

O’Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Lista S et al (2015) Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer’s disease research. Alzheimers Dement 11:549–560. https://doi.org/10.1016/j.jalz.2014.08.099 CrossRefPubMed

269.

O’Bryant SE, Mielke MM, Rissman RA, Lista S, Vanderstichele H, Zetterberg H et al (2017) Blood-based biomarkers in Alzheimer disease: current state of the science and a novel collaborative paradigm for advancing from discovery to clinic. Alzheimers Dement 13:45–58. https://doi.org/10.1016/j.jalz.2016.09.014 CrossRefPubMed

270.

Öhrfelt A, Brinkmalm A, Dumurgier J, Brinkmalm G, Hansson O, Zetterberg H et al (2016) The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease. Alzheimers Res Ther 8:41. https://doi.org/10.1186/s13195-016-0208-8 CrossRefPubMedPubMedCentral

271.

Olsson B, Lautner R, Andreasson U, Öhrfelt A, Portelius E, Bjerke M et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 15:673–684. https://doi.org/10.1016/s1474-4422(16)00070-3 CrossRefPubMed

272.

Olsson F, Schmidt S, Althoff V, Munter LM, Jin S, Rosqvist S et al (2014) Characterization of intermediate steps in amyloid beta (Aβ) production under near-native conditions. J Biol Chem 289:1540–1550. https://doi.org/10.1074/jbc.M113.498246 CrossRefPubMed

273.

Ovod V, Ramsey KN, Mawuenyega KG, Bollinger JG, Hicks T, Schneider T et al (2017) Amyloid β concentrations and stable isotope labeling kinetics of human plasma specific to central nervous system amyloidosis. Alzheimers Dement 13:841–849. https://doi.org/10.1016/j.jalz.2017.06.2266 CrossRefPubMedPubMedCentral

274.

Palmqvist S, Janelidze S, Stromrud E, Zetterberg H, Karl J, Mattsson N et al (2018) Detecting brain amyloid status using fully automated plasma Aβ biomarker assays. Abstract presented at the Alzheimer’s Association International Conference (AAIC) 2018. Chicago (22–26 July 2018)

275.

Palmqvist S, Zetterberg H, Mattsson N, Johansson P, Alzheimer’s Disease Neuroimaging Initiative, Minthon L et al (2015) Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology 85:1240–1249. https://doi.org/10.1212/wnl.0000000000001991

276.

Pannee J, Portelius E, Minthon L, Gobom J, Andreasson U, Zetterberg H et al (2016) Reference measurement procedure for CSF amyloid beta (Aβ)1-42 and the CSF Aβ1-42/Aβ1-40 ratio—a cross-validation study against amyloid PET. J Neurochem 139:651–658. https://doi.org/10.1111/jnc.13838 CrossRefPubMed

277.

Pannee J, Törnqvist U, Westerlund A, Ingelsson M, Lannfelt L, Brinkmalm G et al (2014) The amyloid-β degradation pattern in plasma—a possible tool for clinical trials in Alzheimer’s disease. Neurosci Lett 573:7–12. https://doi.org/10.1016/j.neulet.2014.04.041 CrossRefPubMed

278.

Park JC, Han SH, Cho HJ, Byun MS, Yi D, Choe YM et al (2017) Chemically treated plasma Aβ is a potential blood-based biomarker for screening cerebral amyloid deposition. Alzheimers Res Ther 9:20. https://doi.org/10.1186/s13195-017-0248-8 CrossRefPubMedPubMedCentral

279.

Parnetti L, Eusebi P, Lleó A (2016) Cerebrospinal fluid biomarkers for target engagement and efficacy in clinical trials for Alzheimer’s and Parkinson’s diseases. Front Neurol Neurosci 39:117–123. https://doi.org/10.1159/000445452 CrossRefPubMed

280.

Pascoal TA, Mathotaarachchi S, Shin M, Benedet AL, Mohades S, Wang S et al (2017) Synergistic interaction between amyloid and tau predicts the progression to dementia. Alzheimers Dement 13:644–653. https://doi.org/10.1016/j.jalz.2016.11.005 CrossRefPubMed

281.

Pereira JB, Strandberg TO, Palmqvist S, Volpe G, van Westen D, Westman E et al (2018) Amyloid network topology characterizes the progression of Alzheimer’s disease during the predementia stages. Cereb Cortex 28:340–349. https://doi.org/10.1093/cercor/bhx294 CrossRefPubMed

282.

Pereira JB, Westman E, Hansson O, Alzheimer’s Disease Neuroimaging Initiative (2017) Association between cerebrospinal fluid and plasma neurodegeneration biomarkers with brain atrophy in Alzheimer’s disease. Neurobiol Aging 58:14–29. https://doi.org/10.1016/j.neurobiolaging.2017.06.002 CrossRefPubMed

283.

Perneczky R, Alexopoulos P, Alzheimer’s Disease Neuroimaging Initiative (2014) Cerebrospinal fluid BACE1 activity and markers of amyloid precursor protein metabolism and axonal degeneration in Alzheimer’s disease. Alzheimers Dement 10:S425–S429 e421. https://doi.org/10.1016/j.jalz.2013.09.006

284.

Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele H, Zorzi W et al (2012) Risk of Alzheimer’s disease biological misdiagnosis linked to cerebrospinal collection tubes. J Alzheimers Dis 31:13–20. https://doi.org/10.3233/JAD-2012-120361 CrossRefPubMed

285.

Petersen RC, Aisen P, Boeve BF, Geda YE, Ivnik RJ, Knopman DS et al (2013) Mild cognitive impairment due to Alzheimer disease in the community. Ann Neurol 74:199–208. https://doi.org/10.1002/ana.23931 CrossRefPubMedPubMedCentral

286.

Petzold A, Keir G, Warren J, Fox N, Rossor MN (2007) A systematic review and meta-analysis of CSF neurofilament protein levels as biomarkers in dementia. Neurodegener Dis 4:185–194. https://doi.org/10.1159/000101843 CrossRefPubMed

287.

Piccio L, Deming Y, Del-Águila JL, Ghezzi L, Holtzman DM, Fagan AM et al (2016) Cerebrospinal fluid soluble TREM2 is higher in Alzheimer disease and associated with mutation status. Acta Neuropathol 131:925–933. https://doi.org/10.1007/s00401-016-1533-5 CrossRefPubMedPubMedCentral

288.

Pijnenburg YA, Janssen JC, Schoonenboom NS, Petzold A, Mulder C, Stigbrand T et al (2007) CSF neurofilaments in frontotemporal dementia compared with early onset Alzheimer’s disease and controls. Dement Geriatr Cogn Disord 23:225–230. https://doi.org/10.1159/000099473 CrossRefPubMed

289.

Portelius E, Price E, Brinkmalm G, Stiteler M, Olsson M, Persson R et al (2011) A novel pathway for amyloid precursor protein processing. Neurobiol Aging 32:1090–1098. https://doi.org/10.1016/j.neurobiolaging.2009.06.002 CrossRefPubMed

290.

Portelius E, Westman-Brinkmalm A, Zetterberg H, Blennow K (2006) Determination of β-amyloid peptide signatures in cerebrospinal fluid using immunoprecipitation-mass spectrometry. J Proteome Res 5:1010–1016. https://doi.org/10.1021/pr050475v CrossRefPubMed

291.

Portelius E, Zetterberg H, Skillback T, Tornqvist U, Andreasson U, Trojanowski JQ et al (2015) Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer’s disease. Brain 138:3373–3385. https://doi.org/10.1093/brain/awv267 CrossRefPubMedPubMedCentral

292.

Pottiez G, Yang L, Stewart T, Song N, Aro P, Galasko DR et al (2017) Mass-spectrometry-based method to quantify in parallel tau and amyloid beta 1-42 in CSF for the diagnosis of Alzheimer’s disease. J Proteome Res 16:1228–1238. https://doi.org/10.1021/acs.jproteome.6b00829 CrossRefPubMedPubMedCentral

293.

Querol-Vilaseca M, Colom-Cadena M, Pegueroles J, San Martín-Paniello C, Clarimon J, Belbin O et al (2017) YKL-40 (Chitinase 3-like I) is expressed in a subset of astrocytes in Alzheimer’s disease and other tauopathies. J Neuroinflammation 14:118. https://doi.org/10.1186/s12974-017-0893-7 CrossRefPubMedPubMedCentral

294.

Racine AM, Koscik RL, Nicholas CR, Clark LR, Okonkwo OC, Oh JM et al (2016) Cerebrospinal fluid ratios with Aβ42 predict preclinical brain β-amyloid accumulation. Alzheimers Dement (Amst) 2:27–38. https://doi.org/10.1016/j.dadm.2015.11.006 CrossRef

295.

Reiman EM (2017) Alzheimer disease in 2016: putting AD treatments and biomarkers to the test. Nat Rev Neurol 13:74–76. https://doi.org/10.1038/nrneurol.2017.1 CrossRefPubMed

296.

Rhodin JA, Thomas T (2001) A vascular connection to Alzheimer’s disease. Microcirculation 8:207–220. https://doi.org/10.1038/sj/mn/7800086 CrossRefPubMed

297.

Riemenschneider M, Wagenpfeil S, Vanderstichele H, Otto M, Wiltfang J, Kretzschmar H et al (2003) Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias. Mol Psychiatry 8:343–347. https://doi.org/10.1038/sj.mp.4001220 CrossRefPubMed

298.

Ritter A, Cummings J (2015) Fluid biomarkers in clinical trials of Alzheimer’s disease therapeutics. Front Neurol 6:186. https://doi.org/10.3389/fneur.2015.00186 CrossRefPubMedPubMedCentral

299.

Rivero-Santana A, Ferreira D, Perestelo-Pérez L, Westman E, Wahlund LO, Sarría A et al (2017) Cerebrospinal fluid biomarkers for the differential diagnosis between Alzheimer’s disease and frontotemporal lobar degeneration: systematic review, HSROC analysis, and confounding factors. J Alzheimers Dis 55:625–644. https://doi.org/10.3233/JAD-160366 CrossRefPubMed

300.

Robinson J, Lee E, Xie S, Rennert L, Suh E, Bredenberg C et al (2018) Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain 141:2181–2193. https://doi.org/10.1093/brain/awy146 CrossRefPubMedPubMedCentral

301.

Roe CM, Fagan AM, Grant EA, Hassenstab J, Moulder KL, Maue Dreyfus D et al (2013) Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later. Neurology 80:1784–1791. https://doi.org/10.1212/WNL.0b013e3182918ca6 CrossRefPubMedPubMedCentral

302.

Rojas JC, Karydas A, Bang J, Tsai RM, Blennow K, Liman V et al (2016) Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol 3:216–225. https://doi.org/10.1002/acn3.290 CrossRefPubMedPubMedCentral

303.

Rosén C, Andersson CH, Andreasson U, Molinuevo JL, Bjerke M, Rami L et al (2014) Increased levels of chitotriosidase and YKL-40 in cerebrospinal fluid from patients with Alzheimer’s disease. Dement Geriatr Cogn Dis Extra 4:297–304. https://doi.org/10.1159/000362164 CrossRefPubMedPubMedCentral

304.

Roussos P, Katsel P, Fam P, Tan W, Purohit DP, Haroutunian V (2015) The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer’s dementia. Alzheimers Dement 11:1163–1170. https://doi.org/10.1016/j.jalz.2014.10.013 CrossRefPubMed

305.

Rowe CC, Bourgeat P, Ellis KA, Brown B, Lim YY, Mulligan R et al (2013) Predicting Alzheimer disease with β-amyloid imaging: results from the Australian Imaging, Biomarkers, and Lifestyle Study of Ageing. Ann Neurol 74:905–913. https://doi.org/10.1002/ana.24040 CrossRefPubMed

306.

Russell CL, Mitra V, Hansson K, Blennow K, Gobom J, Zetterberg H et al (2017) Comprehensive quantitative profiling of tau and phosphorylated tau peptides in cerebrospinal fluid by mass spectrometry provides new biomarker candidates. J Alzheimers Dis 55:303–313. https://doi.org/10.3233/JAD-160633 CrossRefPubMed

307.

Salminen A, Kauppinen A, Kaarniranta K (2017) Hypoxia/ischemia activate processing of amyloid precursor protein: impact of vascular dysfunction in the pathogenesis of Alzheimer’s disease. J Neurochem 140:536–549. https://doi.org/10.1111/jnc.13932 CrossRefPubMed

308.

Salvadores N, Shahnawaz M, Scarpini E, Tagliavini F, Soto C (2014) Detection of misfolded Aβ oligomers for sensitive biochemical diagnosis of Alzheimer’s disease. Cell Rep 7:261–268. https://doi.org/10.1016/j.celrep.2014.02.031 CrossRefPubMed

309.

Sanabria-Castro A, Alvarado-Echeverría I, Monge-Bonilla C (2017) Molecular pathogenesis of Alzheimer’s disease: an update. Ann Neurosci 24:46–54. https://doi.org/10.1159/000464422 CrossRefPubMedPubMedCentral

310.

Sanfilippo C, Forlenza O, Zetterberg H, Blennow K (2016) Increased neurogranin concentrations in cerebrospinal fluid of Alzheimer’s disease and in mild cognitive impairment due to AD. J Neural Transm (Vienna) 123:1443–1447. https://doi.org/10.1007/s00702-016-1597-3 CrossRef

311.

Savage MJ, Holder DJ, Wu G, Kaplow J, Siuciak JA, Potter WZ (2015) Soluble BACE-1 activity and sAβPPβ concentrations in Alzheimer’s disease and age-matched healthy control cerebrospinal fluid from the Alzheimer’s Disease Neuroimaging Initiative-1 baseline cohort. J Alzheimers Dis 46:431–440. https://doi.org/10.3233/jad-142778 CrossRefPubMedPubMedCentral

312.

Savage MJ, Kalinina J, Wolfe A, Tugusheva K, Korn R, Cash-Mason T et al (2014) A sensitive aβ oligomer assay discriminates Alzheimer’s and aged control cerebrospinal fluid. J Neurosci 34:2884–2897. https://doi.org/10.1523/JNEUROSCI.1675-13.2014 CrossRefPubMedPubMedCentral

313.

Scheff SW, Price DA, Schmitt FA, Mufson EJ (2006) Hippocampal synaptic loss in early Alzheimer’s disease and mild cognitive impairment. Neurobiol Aging 27:1372–1384. https://doi.org/10.1016/j.neurobiolaging.2005.09.012 CrossRefPubMed

314.

Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S et al (2016) Alzheimer’s disease. Lancet 388:505–517. https://doi.org/10.1016/s0140-6736(15)01124-1 CrossRefPubMed

315.

Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N et al (1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 2:864–870CrossRefPubMed

316.

Schmidt ML, Murray J, Lee VM, Hill WD, Wertkin A, Trojanowski JQ (1991) Epitope map of neurofilament protein domains in cortical and peripheral nervous system Lewy bodies. Am J Pathol 139:53–65PubMedPubMedCentral

317.

Schneider LS, Mangialasche F, Andreasen N, Feldman H, Giacobini E, Jones R et al (2014) Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014. J Intern Med 275:251–283. https://doi.org/10.1111/joim.12191 CrossRefPubMedPubMedCentral

318.

Schuster J, Funke SA (2016) Methods for the specific detection and quantitation of amyloid-β oligomers in cerebrospinal fluid. J Alzheimers Dis 53:53–67. https://doi.org/10.3233/JAD-151029 CrossRefPubMed

319.

Seeburger JL, Holder DJ, Combrinck M, Joachim C, Laterza O, Tanen M et al (2015) Cerebrospinal fluid biomarkers distinguish postmortem-confirmed Alzheimer’s disease from other dementias and healthy controls in the OPTIMA cohort. J Alzheimers Dis 44:525–539. https://doi.org/10.3233/JAD-141725 CrossRefPubMed

320.

Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8:595–608. https://doi.org/10.15252/emmm.201606210 CrossRefPubMedPubMedCentral

321.

Sengupta U, Nilson AN, Kayed R (2016) The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine 6:42–49. https://doi.org/10.1016/j.ebiom.2016.03.035 CrossRefPubMedPubMedCentral

322.

Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D et al (1992) Isolation and quantification of soluble Alzheimer’s β-peptide from biological fluids. Nature 359:325–327. https://doi.org/10.1038/359325a0 CrossRefPubMed

323.

Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M et al (2016) The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature 537:50–56. https://doi.org/10.1038/nature19323 CrossRefPubMed

324.

Shahim P, Zetterberg H, Tegner Y, Blennow K (2017) Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology 88:1788–1794. https://doi.org/10.1212/wnl.0000000000003912 CrossRefPubMedPubMedCentral

325.

Shahnawaz M, Tokuda T, Waragai M, Mendez N, Ishii R, Trenkwalder C et al (2017) Development of a biochemical diagnosis of Parkinson disease by detection of α-synuclein misfolded aggregates in cerebrospinal fluid. JAMA Neurol 74:163–172. https://doi.org/10.1001/jamaneurol.2016.4547 CrossRefPubMed

326.

Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC et al (2009) Cerebrospinal fluid biomarker signature in Alzheimer’s Disease neuroimaging initiative subjects. Ann Neurol 65:403–413. https://doi.org/10.1002/ana.21610 CrossRefPubMedPubMedCentral

327.

Shaw LM, Vanderstichele H, Knapik-Czajka M, Figurski M, Coart E, Blennow K et al (2011) Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI. Acta Neuropathol 121:597–609. https://doi.org/10.1007/s00401-011-0808-0 CrossRefPubMedPubMedCentral

328.

Sheinerman KS, Toledo JB, Tsivinsky VG, Irwin D, Grossman M, Weintraub D et al (2017) Circulating brain-enriched microRNAs as novel biomarkers for detection and differentiation of neurodegenerative diseases. Alzheimers Res Ther 9:89. https://doi.org/10.1186/s13195-017-0316-0 CrossRefPubMedPubMedCentral

329.

Shekhar S, Kumar R, Rai N, Kumar V, Singh K, Upadhyay AD et al (2016) Estimation of tau and phosphorylated tau181 in serum of Alzheimer’s disease and mild cognitive impairment patients. PLoS One 11:e0159099. https://doi.org/10.1371/journal.pone.0159099 CrossRefPubMedPubMedCentral

330.

Shen Y, Wang H, Sun Q, Yao H, Keegan AP, Mullan M et al (2018) Increased plasma beta-secretase 1 may predict conversion to Alzheimer’s disease dementia in individuals with mild cognitive impairment. Biol Psychiatry 83:447–455. https://doi.org/10.1016/j.biopsych.2017.02.007 CrossRefPubMed

331.

Shi M, Zabetian CP, Hancock AM, Ginghina C, Hong Z, Yearout D et al (2010) Significance and confounders of peripheral DJ-1 and alpha-synuclein in Parkinson’s disease. Neurosci Lett 480:78–82. https://doi.org/10.1016/j.neulet.2010.06.009 CrossRefPubMedPubMedCentral

332.

Sims R, van der Lee SJ, Naj AC, Bellenguez C, Badarinarayan N, Jakobsdottir J et al (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer’s disease. Nat Genet 49:1373–1384. https://doi.org/10.1038/ng.3916 CrossRefPubMedPubMedCentral

333.

Singh N, Haldar S, Tripathi AK, Horback K, Wong J, Sharma D et al (2014) Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities. Antioxid Redox Signal 20:1324–1363. https://doi.org/10.1089/ars.2012.4931 CrossRefPubMedPubMedCentral

334.

Sjögren M, Blomberg M, Jonsson M, Wahlund LO, Edman A, Lind K et al (2001) Neurofilament protein in cerebrospinal fluid: a marker of white matter changes. J Neurosci Res 66:510–516. https://doi.org/10.1002/jnr.1242 CrossRefPubMed

335.

Skillbäck T, Farahmand B, Bartlett JW, Rosén C, Mattsson N, Nägga K et al (2014) CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology 83:1945–1953. https://doi.org/10.1212/wnl.0000000000001015 CrossRefPubMed

336.

Skillbäck T, Rosén C, Asztely F, Mattsson N, Blennow K, Zetterberg H (2014) Diagnostic performance of cerebrospinal fluid total tau and phosphorylated tau in Creutzfeldt-Jakob disease: results from the Swedish Mortality Registry. JAMA Neurol 71:476–483. https://doi.org/10.1001/jamaneurol.2013.6455 CrossRefPubMed

337.

Slachevsky A, Guzmán-Martínez L, Delgado C, Reyes P, Farías GA, Muñoz-Neira C et al (2017) Tau platelets correlate with regional brain atrophy in patients with Alzheimer’s disease. J Alzheimers Dis 55:1595–1603. https://doi.org/10.3233/JAD-160652 CrossRefPubMed

338.

Slaets S, Le Bastard N, Martin JJ, Sleegers K, Van Broeckhoven C, De Deyn PP et al (2013) Cerebrospinal fluid Aβ1-40 improves differential dementia diagnosis in patients with intermediate p-tau181 levels. J Alzheimers Dis 36:759–767. https://doi.org/10.3233/jad-130107 CrossRefPubMed

339.

Slaets S, Vanmechelen E, Le Bastard N, Decraemer H, Vandijck M, Martin JJ et al (2014) Increased CSF α-synuclein levels in Alzheimer’s disease: correlation with tau levels. Alzheimers Dement 10:S290–S298. https://doi.org/10.1016/j.jalz.2013.10.004 CrossRefPubMed

340.

Snyder HM, Corriveau RA, Craft S, Faber JE, Greenberg SM, Knopman D et al (2015) Vascular contributions to cognitive impairment and dementia including Alzheimer’s disease. Alzheimers Dement 11:710–717. https://doi.org/10.1016/j.jalz.2014.10.008 CrossRefPubMed

341.

Soares HD, Gasior M, Toyn JH, Wang JS, Hong Q, Berisha F et al (2016) The γ-secretase modulator, BMS-932481, modulates Aβ peptides in the plasma and cerebrospinal fluid of healthy volunteers. J Pharmacol Exp Ther 358:138–150. https://doi.org/10.1124/jpet.116.232256 CrossRefPubMedPubMedCentral

342.

Steardo L Jr, Bronzuoli MR, Iacomino A, Esposito G, Steardo L, Scuderi C (2015) Does neuroinflammation turn on the flame in Alzheimer’s disease? Focus on astrocytes. Front Neurosci 9:259. https://doi.org/10.3389/fnins.2015.00259 CrossRefPubMedPubMedCentral

343.

Strozyk D, Blennow K, White LR, Launer LJ (2003) CSF Aβ 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60:652–656CrossRefPubMed

344.

Suárez-Calvet M, Araque Caballero MÁ, Kleinberger G, Bateman RJ, Fagan AM, Morris JC et al (2016) Early changes in CSF sTREM2 in dominantly inherited Alzheimer’s disease occur after amyloid deposition and neuronal injury. Sci Transl Med 8:369ra178. https://doi.org/10.1126/scitranslmed.aag1767 CrossRefPubMedPubMedCentral

345.

Suárez-Calvet M, Dols-Icardo O, Lladó A, Sánchez-Valle R, Hernández I, Amer G et al (2014) Plasma phosphorylated TDP-43 levels are elevated in patients with frontotemporal dementia carrying a C9orf72 repeat expansion or a GRN mutation. J Neurol Neurosurg Psychiatry 85:684–691. https://doi.org/10.1136/jnnp-2013-305972 CrossRefPubMed

346.

Suárez-Calvet M, Kleinberger G, Araque Caballero MÁ, Brendel M, Rominger A, Alcolea D et al (2016) sTREM2 cerebrospinal fluid levels are a potential biomarker for microglia activity in early-stage Alzheimer’s disease and associate with neuronal injury markers. EMBO Mol Med 8:466–476. https://doi.org/10.15252/emmm.201506123 CrossRefPubMedPubMedCentral

347.

Sutphen CL, McCue L, Herries EM, Xiong C, Ladenson JH, Holtzman DM et al (2018) Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer’s disease. Alzheimers Dement 14:869–879. https://doi.org/10.1016/j.jalz.2018.01.012 CrossRefPubMedPubMedCentral

348.

Suzuki N, Cheung TT, Cai XD, Odaka A, Otvos L Jr, Eckman C et al (1994) An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 264:1336–1340CrossRefPubMed

349.

Suzuki N, Iwatsubo T, Odaka A, Ishibashi Y, Kitada C, Ihara Y (1994) High tissue content of soluble beta 1-40 is linked to cerebral amyloid angiopathy. Am J Pathol 145:452–460PubMedPubMedCentral

350.

Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010) A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 68:930–941. https://doi.org/10.1016/j.biopsych.2010.06.012 CrossRefPubMed

351.

Sze CI, Bi H, Kleinschmidt-DeMasters BK, Filley CM, Martin LJ (2000) Selective regional loss of exocytotic presynaptic vesicle proteins in Alzheimer’s disease brains. J Neurol Sci 175:81–90CrossRefPubMed

352.

Tan YJ, Ng ASL, Vipin A, Lim JKW, Chander RJ, Ji F et al (2017) Higher peripheral TREM2 mRNA levels relate to cognitive deficits and hippocampal atrophy in Alzheimer’s disease and amnestic mild cognitive impairment. J Alzheimers Dis 58:413–423. https://doi.org/10.3233/JAD-161277 CrossRefPubMed

353.

Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H et al (2009) Cerebrospinal fluid β-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol 66:382–389. https://doi.org/10.1001/archneurol.2008.596 CrossRefPubMed

354.

Tarawneh R, D’Angelo G, Crimmins D, Herries E, Griest T, Fagan AM et al (2016) Diagnostic and prognostic utility of the synaptic marker neurogranin in Alzheimer disease. JAMA Neurol 73:561–571. https://doi.org/10.1001/jamaneurol.2016.0086 CrossRefPubMedPubMedCentral

355.

Tarawneh R, D’Angelo G, Macy E, Xiong C, Carter D, Cairns NJ et al (2011) Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease. Ann Neurol 70:274–285. https://doi.org/10.1002/ana.22448 CrossRefPubMedPubMedCentral

356.

Tarawneh R, Head D, Allison S, Buckles V, Fagan AM, Ladenson JH (2015) Cerebrospinal fluid markers of neurodegeneration and rates of brain atrophy in early Alzheimer disease. JAMA Neurol 72:656–665. https://doi.org/10.1001/jamaneurol.2015.0202 CrossRefPubMedPubMedCentral

357.

Tarawneh R, Lee JM, Ladenson JH, Morris JC, Holtzman DM (2012) CSF VILIP-1 predicts rates of cognitive decline in early Alzheimer disease. Neurology 78:709–719. https://doi.org/10.1212/WNL.0b013e318248e568 CrossRefPubMedPubMedCentral

358.

Tatebe H, Kasai T, Ohmichi T, Kishi Y, Kakeya T, Waragai M et al (2017) Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer’s disease and down syndrome. Mol Neurodegener 12:63. https://doi.org/10.1186/s13024-017-0206-8 CrossRefPubMedPubMedCentral

359.

Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580. https://doi.org/10.1002/ana.410300410 CrossRefPubMed

360.

The Ronald and Nancy Reagan Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group (1998) Consensus report of the working group on: “Molecular and biochemical markers of Alzheimer’s disease”. Neurobiol Aging 19:109–116

361.

Thorsell A, Bjerke M, Gobom J, Brunhage E, Vanmechelen E, Andreasen N et al (2010) Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer’s disease. Brain Res 1362:13–22. https://doi.org/10.1016/j.brainres.2010.09.073 CrossRefPubMed

362.

Timmers M, Barão S, Van Broeck B, Tesseur I, Slemmon J, De Waepenaert K et al (2017) BACE1 dynamics upon inhibition with a BACE inhibitor and correlation to downstream Alzheimer’s disease markers in elderly healthy participants. J Alzheimers Dis 56:1437–1449. https://doi.org/10.3233/JAD-160829 CrossRefPubMedPubMedCentral

363.

Tirucherai G, Ahlijanian M, Crowell J, Kolaitis G, Skudalski S, Medlock M (2016) A single ascending dose study of the tau-directed monoclonal antibody BMS-986168. Abstract presented at the 20th International Congress of Parkinson’s Disease and Movement Disorders. Berlin (19–23 June 2016)

364.

Tokuda T, Qureshi MM, Ardah MT, Varghese S, Shehab SA, Kasai T et al (2010) Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 75:1766–1772. https://doi.org/10.1212/WNL.0b013e3181fd613b CrossRefPubMed

365.

Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M et al (2013) Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain 136:2697–2706. https://doi.org/10.1093/brain/awt188 CrossRefPubMedPubMedCentral

366.

Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J (2013) CSF alpha-synuclein improves diagnostic and prognostic performance of CSF tau and Abeta in Alzheimer’s disease. Acta Neuropathol 126:683–697. https://doi.org/10.1007/s00401-013-1148-z CrossRefPubMed

367.

Toledo JB, Xie SX, Trojanowski JQ, Shaw LM (2013) Longitudinal change in CSF tau and Aβ biomarkers for up to 48 months in ADNI. Acta Neuropathol 126:659–670. https://doi.org/10.1007/s00401-013-1151-4 CrossRefPubMed

368.

Toombs J, Paterson RW, Lunn MP, Nicholas JM, Fox NC, Chapman MD et al (2013) Identification of an important potential confound in CSF AD studies: aliquot volume. Clin Chem Lab Med 51:2311–2317. https://doi.org/10.1515/cclm-2013-0293 CrossRefPubMed

369.

Tu S, Okamoto S, Lipton SA, Xu H (2014) Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease. Mol Neurodegener 9:48. https://doi.org/10.1186/1750-1326-9-48 CrossRefPubMedPubMedCentral

370.

Tyson T, Steiner JA, Brundin P (2016) Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology. J Neurochem 139(Suppl 1):275–289. https://doi.org/10.1111/jnc.13449 CrossRefPubMedPubMedCentral

371.

Tzen KY, Yang SY, Chen TF, Cheng TW, Horng HE, Wen HP et al (2014) Plasma Aβ but not tau is related to brain PiB retention in early Alzheimer’s disease. ACS Chem Neurosci 5:830–836. https://doi.org/10.1021/cn500101j CrossRefPubMed

372.

van Bergen JM, Li X, Hua J, Schreiner SJ, Steininger SC, Quevenco FC et al (2016) Colocalization of cerebral iron with amyloid beta in mild cognitive impairment. Sci Rep 6:35514. https://doi.org/10.1038/srep35514 CrossRefPubMedPubMedCentral

373.

van Oijen M, Hofman A, Soares HD, Koudstaal PJ, Breteler MM (2006) Plasma Aβ(1-40) and Aβ(1-42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol 5:655–660. https://doi.org/10.1016/S1474-4422(06)70501-4 CrossRefPubMed

374.

van Rossum IA, Vos S, Handels R, Visser PJ (2010) Biomarkers as predictors for conversion from mild cognitive impairment to Alzheimer-type dementia: implications for trial design. J Alzheimers Dis 20:881–891. https://doi.org/10.3233/JAD-2010-091606 CrossRefPubMed

375.

Vanderstichele H, Bibl M, Engelborghs S, Le Bastard N, Lewczuk P, Molinuevo JL et al (2012) Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer’s disease diagnosis: a consensus paper from the Alzheimer’s Biomarkers Standardization Initiative. Alzheimers Dement 8:65–73. https://doi.org/10.1016/j.jalz.2011.07.004 CrossRefPubMed

376.

Vassar R, Kuhn PH, Haass C, Kennedy ME, Rajendran L, Wong PC et al (2014) Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J Neurochem 130:4–28. https://doi.org/10.1111/jnc.12715 CrossRefPubMedPubMedCentral

377.

Verberk IMW, Slot RE, Verfaillie SCJ, Heijst H, Prins ND, van Berckel BNM et al (2018) Plasma amyloid as prescreener for the earliest Alzheimer pathological changes. Ann Neurol. https://doi.org/10.1002/ana.25334

378.

Vickers JC, Riederer BM, Marugg RA, Buee-Scherrer V, Buee L, Delacourte A et al (1994) Alterations in neurofilament protein immunoreactivity in human hippocampal neurons related to normal aging and Alzheimer’s disease. Neuroscience 62:1–13CrossRefPubMed

379.

Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O et al (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 12:357–367. https://doi.org/10.1016/S1474-4422(13)70044-9 CrossRefPubMed

380.

Vivacqua G, Latorre A, Suppa A, Nardi M, Pietracupa S, Mancinelli R et al (2016) Abnormal salivary total and oligomeric alpha-synuclein in Parkinson’s disease. PLoS One 11:e0151156. https://doi.org/10.1371/journal.pone.0151156 CrossRefPubMedPubMedCentral

381.

Wang MJ, Yi S, Han JY, Park SY, Jang JW, Chun IK et al (2017) Oligomeric forms of amyloid-β protein in plasma as a potential blood-based biomarker for Alzheimer’s disease. Alzheimers Res Ther 9:98. https://doi.org/10.1186/s13195-017-0324-0 CrossRefPubMedPubMedCentral

382.

Wang Y, Shi M, Chung KA, Zabetian CP, Leverenz JB, Berg D et al (2012) Phosphorylated α-synuclein in Parkinson’s disease. Sci Transl Med 4:121ra120. https://doi.org/10.1126/scitranslmed.3002566 CrossRef

383.

Waragai M, Yoshida M, Mizoi M, Saiki R, Kashiwagi K, Takagi K et al (2012) Increased protein-conjugated acrolein and amyloid-β40/42 ratio in plasma of patients with mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis 32:33–41. https://doi.org/10.3233/JAD-2012-120253 CrossRefPubMed

384.

Wennström M, Surova Y, Hall S, Nilsson C, Minthon L, Hansson O et al (2015) The inflammatory marker YKL-40 is elevated in cerebrospinal fluid from patients with Alzheimer’s but not Parkinson’s disease or dementia with Lewy bodies. PLoS One 10:e0135458. https://doi.org/10.1371/journal.pone.0135458 CrossRefPubMedPubMedCentral

385.

Weston PSJ, Poole T, Ryan NS, Nair A, Liang Y, Macpherson K et al (2017) Serum neurofilament light in familial Alzheimer disease: a marker of early neurodegeneration. Neurology 89(21):2167–2175CrossRefPubMedPubMedCentral

386.

Willemse E, van Uffelen K, Brix B, Engelborghs S, Vanderstichele H, Teunissen C (2017) How to handle adsorption of cerebrospinal fluid amyloid β (1-42) in laboratory practice? Identifying problematic handlings and resolving the issue by use of the Aβ42/Aβ40 ratio. Alzheimers Dement 13:885–892. https://doi.org/10.1016/j.jalz.2017.01.010 CrossRefPubMed

387.

Williams SM, Schulz P, Rosenberry TL, Caselli RJ, Sierks MR (2017) Blood-based oligomeric and other protein variant biomarkers to facilitate pre-symptomatic diagnosis and staging of Alzheimer’s disease. J Alzheimers Dis 58:23–35. https://doi.org/10.3233/jad-161116 CrossRefPubMed

388.

Wiltfang J, Esselmann H, Bibl M, Hüll M, Hampel H, Kessler H et al (2007) Amyloid β peptide ratio 42/40 but not Aβ42 correlates with phospho-tau in patients with low- and high-CSF Aβ40 load. J Neurochem 101:1053–1059. https://doi.org/10.1111/j.1471-4159.2006.04404.x CrossRefPubMed

389.

Winston CN, Goetzl EJ, Akers JC, Carter BS, Rockenstein EM, Galasko D et al (2016) Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile. Alzheimers Dement (Amst) 3:63–72. https://doi.org/10.1016/j.dadm.2016.04.001 CrossRef

390.

Wiseman FK, Al-Janabi T, Hardy J, Karmiloff-Smith A, Nizetic D, Tybulewicz VL et al (2015) A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome. Nat Rev Neurosci 16:564–574. https://doi.org/10.1038/nrn3983 CrossRefPubMedPubMedCentral

391.

World Health Organization (2017) Dementia factsheet. http://www.who.int/mediacentre/factsheets/fs362/en/. Accessed August 2017

392.

Wu G, Sankaranarayanan S, Tugusheva K, Kahana J, Seabrook G, Shi XP et al (2008) Decrease in age-adjusted cerebrospinal fluid β-secretase activity in Alzheimer’s subjects. Clin Biochem 41:986–996. https://doi.org/10.1016/j.clinbiochem.2008.04.022 CrossRefPubMed

393.

Wu G, Sankaranarayanan S, Wong J, Tugusheva K, Michener MS, Shi X et al (2012) Characterization of plasma β-secretase (BACE1) activity and soluble amyloid precursor proteins as potential biomarkers for Alzheimer’s disease. J Neurosci Res 90:2247–2258. https://doi.org/10.1002/jnr.23122 CrossRefPubMed

394.

Yan R (2017) Physiological functions of the β-site amyloid precursor protein cleaving enzyme 1 and 2. Front Mol Neurosci 10:97. https://doi.org/10.3389/fnmol.2017.00097 CrossRefPubMedPubMedCentral

395.

Yang CC, Chiu MJ, Chen TF, Chang HL, Liu BH, Yang SY (2018) Assay of plasma phosphorylated tau protein (threonine 181) and total tau protein in early-stage Alzheimer’s disease. J Alzheimers Dis 61:1323–1332. https://doi.org/10.3233/JAD-170810 CrossRefPubMed

396.

Yang T, O’Malley TT, Kanmert D, Jerecic J, Zieske LR, Zetterberg H et al (2015) A highly sensitive novel immunoassay specifically detects low levels of soluble Abeta oligomers in human cerebrospinal fluid. Alzheimers Res Ther 7:14. https://doi.org/10.1186/s13195-015-0100-y CrossRefPubMedPubMedCentral

397.

Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC et al (2007) Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53:337–351. https://doi.org/10.1016/j.neuron.2007.01.010 CrossRefPubMed

398.

Yuan A, Rao MV, Veeranna Nixon RA (2012) Neurofilaments at a glance. J Cell Sci 125:3257–3263. https://doi.org/10.1242/jcs.104729 CrossRefPubMedPubMedCentral

399.

Yuan A, Rao MV, Veeranna Nixon RA (2017) Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harb Perspect Biol 9:a018309. https://doi.org/10.1101/cshperspect.a018309 CrossRefPubMedPubMedCentral

400.

Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM et al (2016) TREM2 haplodeficiency in mice and humans impairs the microglia barrier function leading to decreased amyloid compaction and severe axonal dystrophy. Neuron 92:252–264. https://doi.org/10.1016/j.neuron.2016.09.016 CrossRefPubMed

401.

Zetterberg H, Andreasson U, Hansson O, Wu G, Sankaranarayanan S, Andersson ME et al (2008) Elevated cerebrospinal fluid BACE1 activity in incipient Alzheimer disease. Arch Neurol 65:1102–1107. https://doi.org/10.1001/archneur.65.8.1102 CrossRefPubMed

402.

Zetterberg H, Pedersen M, Lind K, Svensson M, Rolstad S, Eckerström C et al (2007) Intra-individual stability of CSF biomarkers for Alzheimer’s disease over two years. J Alzheimers Dis 12:255–260CrossRefPubMed

403.

Zetterberg H, Skillbäck T, Mattsson N, Trojanowski JQ, Portelius E, Shaw LM et al (2016) Association of cerebrospinal fluid neurofilament light concentration with Alzheimer disease progression. JAMA Neurol 73:60–67. https://doi.org/10.1001/jamaneurol.2015.3037 CrossRefPubMedPubMedCentral

404.

Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J et al (2013) Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther 5:9. https://doi.org/10.1186/alzrt163 CrossRefPubMedPubMedCentral

405.

Zhang B, Carroll J, Trojanowski JQ, Yao Y, Iba M, Potuzak JS et al (2012) The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic mice. J Neurosci 32:3601–3611. https://doi.org/10.1523/jneurosci.4922-11.2012 CrossRefPubMedPubMedCentral

406.

Zhang QS, Heng Y, Yuan YH, Chen NH (2017) Pathological α-synuclein exacerbates the progression of Parkinson’s disease through microglial activation. Toxicol Lett 265:30–37. https://doi.org/10.1016/j.toxlet.2016.11.002 CrossRefPubMed

407.

Zhong Z, Ewers M, Teipel S, Bürger K, Wallin A, Blennow K et al (2007) Levels of β-secretase (BACE1) in cerebrospinal fluid as a predictor of risk in mild cognitive impairment. Arch Gen Psychiatry 64:718–726. https://doi.org/10.1001/archpsyc.64.6.718 CrossRefPubMed

408.

Zhou W, Zhang J, Ye F, Xu G, Su H, Su Y et al (2017) Plasma neurofilament light chain levels in Alzheimer’s disease. Neurosci Lett 650:60–64. https://doi.org/10.1016/j.neulet.2017.04.027 CrossRefPubMed

At a glance: The STEP trials

Springer Medicine

Current state of Alzheimer’s fluid biomarkers

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2018

Mutant superoxide dismutase aggregates from human spinal cord transmit amyotrophic lateral sclerosis

Astrocytic degeneration in chronic traumatic encephalopathy

Sex differences in Alzheimer’s disease and common neuropathologies of aging

Differential impact of pure glyphosate and glyphosate-based herbicide in a model of peripheral nervous system myelination

Chordoid meningiomas can be sub-stratified into prognostically distinct DNA methylation classes and are enriched for heterozygous deletions of chromosomal arm 2p

Evidence of intraneuronal Aβ accumulation preceding tau pathology in the entorhinal cortex