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Published in: Neurology and Therapy 1/2017

Open Access 01-07-2017 | Review

A Review of Fluid Biomarkers for Alzheimer’s Disease: Moving from CSF to Blood

Author: Kaj Blennow

Published in: Neurology and Therapy | Special Issue 1/2017

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Abstract

A set of core cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease (AD) includes total tau (T-tau), phosphorylated tau (P-tau) and β-amyloid 42 (Aβ42). These biomarkers reflect some of the key aspects of AD pathophysiology, including neuronal degeneration, tau phosphorylation with tangle formation, and Aβ aggregation with deposition of the peptide into plaques. The core AD CSF biomarkers have been validated clinically in numerous studies, and found to have a very high diagnostic performance to identify AD, both in the dementia and in the mild cognitive impairment stages of the disease. CSF Aβ42 has also been found to show very high concordance with amyloid PET to identify brain amyloid deposition. The synaptic protein neurogranin is a novel candidate CSF biomarker for AD and prodromal AD. High CSF neurogranin predicts future cognitive decline and seems to be more specific for AD than, for example, T-tau. Importantly, technical developments have given ultrasensitive measurement techniques that allow measurement of brain-specific proteins such as tau and neurofilament light (NFL) in blood samples. Both plasma tau and NFL are increased in AD, and a recent study showed that plasma NFL has a diagnostic performance comparable to the core AD CSF biomarkers, and predicted future cognitive decline. Future large longitudinal clinical studies are warranted to determine the potential for plasma tau and NFL to serve as first-in-line screening tools for neurodegeneration in primary care.
Literature
1.
go back to reference Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6(3):131–44.CrossRefPubMed Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6(3):131–44.CrossRefPubMed
2.
go back to reference Beastall GH, Watson ID. Clinical Chemistry and Laboratory Medicine: an appreciation. Clin Chem Lab Med CCLM/FESCC. 2013;51(1):3–4. Beastall GH, Watson ID. Clinical Chemistry and Laboratory Medicine: an appreciation. Clin Chem Lab Med CCLM/FESCC. 2013;51(1):3–4.
3.
go back to reference Blennow K, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2(10):605–13.CrossRefPubMed Blennow K, Hampel H. CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2(10):605–13.CrossRefPubMed
4.
go back to reference Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol. 1995;26(3):231–45.CrossRefPubMed Blennow K, Wallin A, Agren H, Spenger C, Siegfried J, Vanmechelen E. Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease? Mol Chem Neuropathol. 1995;26(3):231–45.CrossRefPubMed
5.
go back to reference Vanmechelen E, Vanderstichele H, Davidsson P, Van Kerschaver E, Van Der Perre B, Sjogren M, et al. Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization. Neurosci Lett. 2000;285(1):49–52.CrossRefPubMed Vanmechelen E, Vanderstichele H, Davidsson P, Van Kerschaver E, Van Der Perre B, Sjogren M, et al. Quantification of tau phosphorylated at threonine 181 in human cerebrospinal fluid: a sandwich ELISA with a synthetic phosphopeptide for standardization. Neurosci Lett. 2000;285(1):49–52.CrossRefPubMed
6.
go back to reference Andreasen N, Minthon L, Clarberg A, Davidsson P, Gottfries J, Vanmechelen E, et al. Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample. Neurology. 1999;53(7):1488–94.CrossRefPubMed Andreasen N, Minthon L, Clarberg A, Davidsson P, Gottfries J, Vanmechelen E, et al. Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample. Neurology. 1999;53(7):1488–94.CrossRefPubMed
7.
go back to reference Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673–84.CrossRefPubMed Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E, Bjerke M, et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol. 2016;15(7):673–84.CrossRefPubMed
8.
go back to reference Koopman K, Le Bastard N, Martin JJ, Nagels G, De Deyn PP, Engelborghs S. Improved discrimination of autopsy-confirmed Alzheimer’s disease (AD) from non-AD dementias using CSF P-tau (181P). Neurochem Int. 2009;55(4):214–8.CrossRefPubMed Koopman K, Le Bastard N, Martin JJ, Nagels G, De Deyn PP, Engelborghs S. Improved discrimination of autopsy-confirmed Alzheimer’s disease (AD) from non-AD dementias using CSF P-tau (181P). Neurochem Int. 2009;55(4):214–8.CrossRefPubMed
9.
go back to reference Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65(4):403–13.CrossRefPubMedPubMedCentral Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65(4):403–13.CrossRefPubMedPubMedCentral
10.
go back to reference Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, et al. The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement J Alzheimers Assoc. 2011;7(4):386–95 (e6).CrossRef Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, et al. The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement J Alzheimers Assoc. 2011;7(4):386–95 (e6).CrossRef
11.
go back to reference Leinenbach A, Pannee J, Dulffer T, Huber A, Bittner T, Andreasson U, et al. Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-beta in cerebrospinal fluid. Clin Chem. 2014;60(7):987–94.CrossRefPubMed Leinenbach A, Pannee J, Dulffer T, Huber A, Bittner T, Andreasson U, et al. Mass spectrometry-based candidate reference measurement procedure for quantification of amyloid-beta in cerebrospinal fluid. Clin Chem. 2014;60(7):987–94.CrossRefPubMed
12.
go back to reference Kuhlmann J, Andreasson U, Pannee J, Bjerke M, Portelius E, Leinenbach A, et al. CSF Abeta1-42—an excellent but complicated Alzheimer’s biomarker: a route to standardisation. Clin Chim Acta. 2017;467:27–33.CrossRefPubMed Kuhlmann J, Andreasson U, Pannee J, Bjerke M, Portelius E, Leinenbach A, et al. CSF Abeta1-42—an excellent but complicated Alzheimer’s biomarker: a route to standardisation. Clin Chim Acta. 2017;467:27–33.CrossRefPubMed
13.
go back to reference Bittner T, Zetterberg H, Teunissen CE, Ostlund RE Jr, Militello M, Andreasson U, et al. Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of beta-amyloid (1–42) in human cerebrospinal fluid. Alzheimers Dement. 2016;12(5):517–26.CrossRefPubMed Bittner T, Zetterberg H, Teunissen CE, Ostlund RE Jr, Militello M, Andreasson U, et al. Technical performance of a novel, fully automated electrochemiluminescence immunoassay for the quantitation of beta-amyloid (1–42) in human cerebrospinal fluid. Alzheimers Dement. 2016;12(5):517–26.CrossRefPubMed
14.
go back to reference Andreasen N, Minthon L, Vanmechelen E, Vanderstichele H, Davidsson P, Winblad B, et al. Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment. Neurosci Lett. 1999;273(1):5–8.CrossRefPubMed Andreasen N, Minthon L, Vanmechelen E, Vanderstichele H, Davidsson P, Winblad B, et al. Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer’s disease in patients with mild cognitive impairment. Neurosci Lett. 1999;273(1):5–8.CrossRefPubMed
15.
go back to reference Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5(3):228–34.CrossRefPubMed Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5(3):228–34.CrossRefPubMed
16.
go back to reference Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y, et al. Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009;8(7):619–27.CrossRefPubMed Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y, et al. Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009;8(7):619–27.CrossRefPubMed
17.
go back to reference Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA J Am Med Assoc. 2009;302(4):385–93.CrossRef Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA J Am Med Assoc. 2009;302(4):385–93.CrossRef
18.
go back to reference May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, et al. The potent BACE1 inhibitor LY2886721 elicits robust central Abeta pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015;35(3):1199–210.CrossRefPubMed May PC, Willis BA, Lowe SL, Dean RA, Monk SA, Cocke PJ, et al. The potent BACE1 inhibitor LY2886721 elicits robust central Abeta pharmacodynamic responses in mice, dogs, and humans. J Neurosci. 2015;35(3):1199–210.CrossRefPubMed
19.
go back to reference Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature. 2016;537(7618):50–6.CrossRefPubMed Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Nature. 2016;537(7618):50–6.CrossRefPubMed
20.
go back to reference Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J, et al. Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov. 2010;9(7):560–74.CrossRefPubMed Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J, et al. Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov. 2010;9(7):560–74.CrossRefPubMed
21.
go back to reference Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734–46.CrossRefPubMed Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734–46.CrossRefPubMed
22.
go back to reference Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.CrossRefPubMed Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13(6):614–29.CrossRefPubMed
23.
go back to reference Blennow K, Mattsson N, Scholl M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol Sci. 2015;36(5):297–309.CrossRefPubMed Blennow K, Mattsson N, Scholl M, Hansson O, Zetterberg H. Amyloid biomarkers in Alzheimer’s disease. Trends Pharmacol Sci. 2015;36(5):297–309.CrossRefPubMed
24.
go back to reference Palmqvist S, Zetterberg H, Blennow K, Vestberg S, Andreasson U, Brooks DJ, et al. Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid beta-amyloid 42: a cross-validation study against amyloid positron emission tomography. JAMA Neurol. 2014;71(10):1282–9.CrossRefPubMed Palmqvist S, Zetterberg H, Blennow K, Vestberg S, Andreasson U, Brooks DJ, et al. Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid beta-amyloid 42: a cross-validation study against amyloid positron emission tomography. JAMA Neurol. 2014;71(10):1282–9.CrossRefPubMed
25.
go back to reference Mattsson N, Insel PS, Landau S, Jagust W, Donohue M, Shaw LM, et al. Diagnostic accuracy of CSF Ab42 and florbetapir PET for Alzheimer’s disease. Ann Clin Transl Neurol. 2014;1(8):534–43.CrossRefPubMedPubMedCentral Mattsson N, Insel PS, Landau S, Jagust W, Donohue M, Shaw LM, et al. Diagnostic accuracy of CSF Ab42 and florbetapir PET for Alzheimer’s disease. Ann Clin Transl Neurol. 2014;1(8):534–43.CrossRefPubMedPubMedCentral
26.
go back to reference Mattsson N, Insel PS, Donohue M, Landau S, Jagust WJ, Shaw LM, et al. Independent information from cerebrospinal fluid amyloid-beta and florbetapir imaging in Alzheimer’s disease. Brain. 2015;138(Pt 3):772–83.CrossRefPubMed Mattsson N, Insel PS, Donohue M, Landau S, Jagust WJ, Shaw LM, et al. Independent information from cerebrospinal fluid amyloid-beta and florbetapir imaging in Alzheimer’s disease. Brain. 2015;138(Pt 3):772–83.CrossRefPubMed
27.
go back to reference Palmqvist S, Zetterberg H, Mattsson N, Johansson P, Alzheimer’s Disease Neuroimaging I, Minthon L, et al. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology. 2015;85(14):1240–9.CrossRefPubMedPubMedCentral Palmqvist S, Zetterberg H, Mattsson N, Johansson P, Alzheimer’s Disease Neuroimaging I, Minthon L, et al. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology. 2015;85(14):1240–9.CrossRefPubMedPubMedCentral
28.
go back to reference Buchhave P, Minthon L, Zetterberg H, Wallin AK, Blennow K, Hansson O. Cerebrospinal fluid levels of beta-amyloid 1–42, but not of tau, are fully changed already 5–10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012;69(1):98–106.CrossRefPubMed Buchhave P, Minthon L, Zetterberg H, Wallin AK, Blennow K, Hansson O. Cerebrospinal fluid levels of beta-amyloid 1–42, but not of tau, are fully changed already 5–10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012;69(1):98–106.CrossRefPubMed
29.
go back to reference van Rossum IA, Vos SJ, Burns L, Knol DL, Scheltens P, Soininen H, et al. Injury markers predict time to dementia in subjects with MCI and amyloid pathology. Neurology. 2012;79(17):1809–16.CrossRefPubMedPubMedCentral van Rossum IA, Vos SJ, Burns L, Knol DL, Scheltens P, Soininen H, et al. Injury markers predict time to dementia in subjects with MCI and amyloid pathology. Neurology. 2012;79(17):1809–16.CrossRefPubMedPubMedCentral
30.
go back to reference Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30(4):572–80.CrossRefPubMed Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30(4):572–80.CrossRefPubMed
31.
go back to reference DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol. 1990;27(5):457–64.CrossRefPubMed DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol. 1990;27(5):457–64.CrossRefPubMed
32.
go back to reference Bittner T, Burgold S, Dorostkar MM, Fuhrmann M, Wegenast-Braun BM, Schmidt B, et al. Amyloid plaque formation precedes dendritic spine loss. Acta Neuropathol. 2012;124(6):797–807.CrossRefPubMedPubMedCentral Bittner T, Burgold S, Dorostkar MM, Fuhrmann M, Wegenast-Braun BM, Schmidt B, et al. Amyloid plaque formation precedes dendritic spine loss. Acta Neuropathol. 2012;124(6):797–807.CrossRefPubMedPubMedCentral
33.
go back to reference Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27(11):2866–75.CrossRefPubMed Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27(11):2866–75.CrossRefPubMed
34.
go back to reference Zou C, Montagna E, Shi Y, Peters F, Blazquez-Llorca L, Shi S, et al. Intraneuronal APP and extracellular Abeta independently cause dendritic spine pathology in transgenic mouse models of Alzheimer’s disease. Acta Neuropathol. 2015;129(6):909–20.CrossRefPubMedPubMedCentral Zou C, Montagna E, Shi Y, Peters F, Blazquez-Llorca L, Shi S, et al. Intraneuronal APP and extracellular Abeta independently cause dendritic spine pathology in transgenic mouse models of Alzheimer’s disease. Acta Neuropathol. 2015;129(6):909–20.CrossRefPubMedPubMedCentral
35.
go back to reference Dickstein DL, Brautigam H, Stockton SD Jr, Schmeidler J, Hof PR. Changes in dendritic complexity and spine morphology in transgenic mice expressing human wild-type tau. Brain Struct Funct. 2010;214(2–3):161–79.CrossRefPubMedPubMedCentral Dickstein DL, Brautigam H, Stockton SD Jr, Schmeidler J, Hof PR. Changes in dendritic complexity and spine morphology in transgenic mice expressing human wild-type tau. Brain Struct Funct. 2010;214(2–3):161–79.CrossRefPubMedPubMedCentral
36.
go back to reference Bellucci A, Westwood AJ, Ingram E, Casamenti F, Goedert M, Spillantini MG. Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am J Pathol. 2004;165(5):1643–52.CrossRefPubMedPubMedCentral Bellucci A, Westwood AJ, Ingram E, Casamenti F, Goedert M, Spillantini MG. Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein. Am J Pathol. 2004;165(5):1643–52.CrossRefPubMedPubMedCentral
37.
go back to reference Represa A, Deloulme JC, Sensenbrenner M, Ben-Ari Y, Baudier J. Neurogranin: immunocytochemical localization of a brain-specific protein kinase C substrate. J Neurosci. 1990;10(12):3782–92.PubMed Represa A, Deloulme JC, Sensenbrenner M, Ben-Ari Y, Baudier J. Neurogranin: immunocytochemical localization of a brain-specific protein kinase C substrate. J Neurosci. 1990;10(12):3782–92.PubMed
38.
go back to reference Guadano-Ferraz A, Vinuela A, Oeding G, Bernal J, Rausell E. RC3/neurogranin is expressed in pyramidal neurons of motor and somatosensory cortex in normal and denervated monkeys. J Comp Neurol. 2005;493(4):554–70.CrossRefPubMed Guadano-Ferraz A, Vinuela A, Oeding G, Bernal J, Rausell E. RC3/neurogranin is expressed in pyramidal neurons of motor and somatosensory cortex in normal and denervated monkeys. J Comp Neurol. 2005;493(4):554–70.CrossRefPubMed
39.
go back to reference Fedorov NB, Pasinelli P, Oestreicher AB, DeGraan PN, Reymann KG. Antibodies to postsynaptic PKC substrate neurogranin prevent long-term potentiation in hippocampal CA1 neurons. Eur J Neurosci. 1995;7(4):819–22.CrossRefPubMed Fedorov NB, Pasinelli P, Oestreicher AB, DeGraan PN, Reymann KG. Antibodies to postsynaptic PKC substrate neurogranin prevent long-term potentiation in hippocampal CA1 neurons. Eur J Neurosci. 1995;7(4):819–22.CrossRefPubMed
40.
go back to reference Chen SJ, Sweatt JD, Klann E. Enhanced phosphorylation of the postsynaptic protein kinase C substrate RC3/neurogranin during long-term potentiation. Brain Res. 1997;749(2):181–7.CrossRefPubMed Chen SJ, Sweatt JD, Klann E. Enhanced phosphorylation of the postsynaptic protein kinase C substrate RC3/neurogranin during long-term potentiation. Brain Res. 1997;749(2):181–7.CrossRefPubMed
41.
go back to reference Davidsson P, Blennow K. Neurochemical dissection of synaptic pathology in Alzheimer’s disease. Int Psychogeriatr IPA. 1998;10(1):11–23.CrossRef Davidsson P, Blennow K. Neurochemical dissection of synaptic pathology in Alzheimer’s disease. Int Psychogeriatr IPA. 1998;10(1):11–23.CrossRef
42.
go back to reference Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell W Jr, et al. Differential loss of synaptic proteins in Alzheimer’s disease: implications for synaptic dysfunction. J Alzheimers Dis JAD. 2005;7(2):103–17 (discussion 73–80).CrossRefPubMed Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell W Jr, et al. Differential loss of synaptic proteins in Alzheimer’s disease: implications for synaptic dysfunction. J Alzheimers Dis JAD. 2005;7(2):103–17 (discussion 73–80).CrossRefPubMed
43.
go back to reference Thorsell A, Bjerke M, Gobom J, Brunhage E, Vanmechelen E, Andreasen N, et al. Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer’s disease. Brain Res. 2010;1362:13–22.CrossRefPubMed Thorsell A, Bjerke M, Gobom J, Brunhage E, Vanmechelen E, Andreasen N, et al. Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer’s disease. Brain Res. 2010;1362:13–22.CrossRefPubMed
44.
go back to reference Kvartsberg H, Duits FH, Ingelsson M, Andreasen N, Ohrfelt A, Andersson K, et al. Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer’s disease. Alzheimers Dement. 2015;11(10):1180–90.CrossRefPubMed Kvartsberg H, Duits FH, Ingelsson M, Andreasen N, Ohrfelt A, Andersson K, et al. Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer’s disease. Alzheimers Dement. 2015;11(10):1180–90.CrossRefPubMed
45.
go back to reference Hellwig K, Kvartsberg H, Portelius E, Andreasson U, Oberstein TJ, Lewczuk P, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther. 2015;7:74.CrossRefPubMedPubMedCentral Hellwig K, Kvartsberg H, Portelius E, Andreasson U, Oberstein TJ, Lewczuk P, et al. Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease. Alzheimers Res Ther. 2015;7:74.CrossRefPubMedPubMedCentral
46.
go back to reference Kvartsberg H, Portelius E, Andreasson U, Brinkmalm G, Hellwig K, Lelental N, et al. Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer’s disease patients and healthy controls. Alzheimers Res Ther. 2015;7(1):40.CrossRefPubMedPubMedCentral Kvartsberg H, Portelius E, Andreasson U, Brinkmalm G, Hellwig K, Lelental N, et al. Characterization of the postsynaptic protein neurogranin in paired cerebrospinal fluid and plasma samples from Alzheimer’s disease patients and healthy controls. Alzheimers Res Ther. 2015;7(1):40.CrossRefPubMedPubMedCentral
47.
go back to reference Portelius E, Zetterberg H, Skillback T, Tornqvist U, Andreasson U, Trojanowski JQ, et al. Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer’s disease. Brain J Neurol. 2015;138(Pt 11):3373–85.CrossRef Portelius E, Zetterberg H, Skillback T, Tornqvist U, Andreasson U, Trojanowski JQ, et al. Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer’s disease. Brain J Neurol. 2015;138(Pt 11):3373–85.CrossRef
48.
go back to reference Wellington H, Paterson RW, Portelius E, Tornqvist U, Magdalinou N, Fox NC, et al. Increased CSF neurogranin concentration is specific to Alzheimer disease. Neurology. 2016;86(9):829–35.CrossRefPubMedPubMedCentral Wellington H, Paterson RW, Portelius E, Tornqvist U, Magdalinou N, Fox NC, et al. Increased CSF neurogranin concentration is specific to Alzheimer disease. Neurology. 2016;86(9):829–35.CrossRefPubMedPubMedCentral
49.
go back to reference Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P, et al. Neurogranin, a CSF biomarker for synaptic loss, predicts decline to symptomatic Alzheimer disease. JAMA Neurol. 2015; (In press). Kester MI, Teunissen CE, Crimmins DL, Herries EM, Ladenson JH, Scheltens P, et al. Neurogranin, a CSF biomarker for synaptic loss, predicts decline to symptomatic Alzheimer disease. JAMA Neurol. 2015; (In press).
50.
go back to reference Sjogren M, Vanderstichele H, Agren H, Zachrisson O, Edsbagge M, Wikkelso C, et al. Tau and Abeta42 in cerebrospinal fluid from healthy adults 21–93 years of age: establishment of reference values. Clin Chem. 2001;47(10):1776–81.PubMed Sjogren M, Vanderstichele H, Agren H, Zachrisson O, Edsbagge M, Wikkelso C, et al. Tau and Abeta42 in cerebrospinal fluid from healthy adults 21–93 years of age: establishment of reference values. Clin Chem. 2001;47(10):1776–81.PubMed
51.
go back to reference Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J, et al. Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther. 2013;5(2):9.CrossRefPubMedPubMedCentral Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J, et al. Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther. 2013;5(2):9.CrossRefPubMedPubMedCentral
52.
go back to reference Blennow K, Fredman P, Wallin A, Gottfries CG, Karlsson I, Langstrom G, et al. Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18–88 years of age. Eur Neurol. 1993;33(2):129–33.CrossRefPubMed Blennow K, Fredman P, Wallin A, Gottfries CG, Karlsson I, Langstrom G, et al. Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18–88 years of age. Eur Neurol. 1993;33(2):129–33.CrossRefPubMed
53.
go back to reference Andreasson U, Blennow K, Zetterberg H. Update on ultrasensitive technologies to facilitate research on blood biomarkers for central nervous system disorders. Alzheimers Dement (Amst). 2016;3:98–102.PubMedPubMedCentral Andreasson U, Blennow K, Zetterberg H. Update on ultrasensitive technologies to facilitate research on blood biomarkers for central nervous system disorders. Alzheimers Dement (Amst). 2016;3:98–102.PubMedPubMedCentral
54.
go back to reference Tzen KY, Yang SY, Chen TF, Cheng TW, Horng HE, Wen HP, et al. Plasma Abeta but not tau is related to brain PiB retention in early Alzheimer’s disease. ACS Chem Neurosci. 2014;5(9):830–6.CrossRefPubMed Tzen KY, Yang SY, Chen TF, Cheng TW, Horng HE, Wen HP, et al. Plasma Abeta but not tau is related to brain PiB retention in early Alzheimer’s disease. ACS Chem Neurosci. 2014;5(9):830–6.CrossRefPubMed
55.
56.
go back to reference Gisslen M, Price RW, Andreasson U, Norgren N, Nilsson S, Hagberg L, et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine. 2016;3:135–40.CrossRefPubMed Gisslen M, Price RW, Andreasson U, Norgren N, Nilsson S, Hagberg L, et al. Plasma concentration of the neurofilament light protein (NFL) is a biomarker of CNS injury in HIV infection: a cross-sectional study. EBioMedicine. 2016;3:135–40.CrossRefPubMed
57.
go back to reference Kuhle J, Barro C, Andreasson U, Derfuss T, Lindberg R, Sandelius A, et al. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med. 2016;54(10):1655–61.CrossRefPubMed Kuhle J, Barro C, Andreasson U, Derfuss T, Lindberg R, Sandelius A, et al. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med. 2016;54(10):1655–61.CrossRefPubMed
58.
go back to reference Mattsson N, Andreasson U, Zetterberg H, Blennow K. Alzheimer’s disease neuroimaging I. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2017;74:557–66.CrossRefPubMed Mattsson N, Andreasson U, Zetterberg H, Blennow K. Alzheimer’s disease neuroimaging I. Association of plasma neurofilament light with neurodegeneration in patients with Alzheimer disease. JAMA Neurol. 2017;74:557–66.CrossRefPubMed
59.
go back to reference Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, et al. Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology. 2016;87(13):1329–36.CrossRefPubMedPubMedCentral Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, et al. Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology. 2016;87(13):1329–36.CrossRefPubMedPubMedCentral
60.
go back to reference Rojas JC, Karydas A, Bang J, Tsai RM, Blennow K, Liman V, et al. Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol. 2016;3(3):216–25.CrossRefPubMedPubMedCentral Rojas JC, Karydas A, Bang J, Tsai RM, Blennow K, Liman V, et al. Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol. 2016;3(3):216–25.CrossRefPubMedPubMedCentral
Metadata
Title
A Review of Fluid Biomarkers for Alzheimer’s Disease: Moving from CSF to Blood
Author
Kaj Blennow
Publication date
01-07-2017
Publisher
Springer Healthcare
Published in
Neurology and Therapy / Issue Special Issue 1/2017
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI
https://doi.org/10.1007/s40120-017-0073-9

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