Top

Published in:

Open Access 01-12-2024 | Alzheimer's Disease | Research

Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis

Authors: Zhen Guo, Chen Tian, Yang Shi, Xue-Ru Song, Wei Yin, Qing-Qing Tao, Jie Liu, Guo-Ping Peng, Zhi-Ying Wu, Yan-Jiang Wang, Zhen-Xin Zhang, Jing Zhang

Published in: Acta Neuropathologica Communications | Issue 1/2024

Abstract

Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer’s disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers. The performance of GABRD and GPR162, along with the AD molecule pTau217, was tested using the self-developed and optimized nanoflow cytometry-based technology, which not only detected the positive ratio of EVs but also concurrently presented the corresponding particle size of the EVs, in discovery (n = 310) and validation (n = 213) cohorts. Plasma GABRD⁺- or GPR162⁺-carrying pTau217-EVs were significantly reduced in AD compared with healthy control (HC). Additionally, the size distribution of GABRD⁺- and GPR162⁺-carrying pTau217-EVs were significantly different between AD and non-AD dementia (NAD). An integrative model, combining age, the number and corresponding size of the distribution of GABRD⁺- or GPR162⁺-carrying pTau217-EVs, accurately and sensitively discriminated AD from HC [discovery cohort, area under the curve (AUC) = 0.96; validation cohort, AUC = 0.93] and effectively differentiated AD from NAD (discovery cohort, AUC = 0.91; validation cohort, AUC = 0.90). This study showed that brain regionally enriched neuronal EVs carrying pTau217 in plasma may serve as a robust diagnostic and differential diagnostic tool in both clinical practice and trials for AD.

Available only for authorised users

Agliardi C, Guerini FR, Zanzottera M, Bianchi A, Nemni R, Clerici M (2019) SNAP-25 in serum is carried by exosomes of neuronal origin and is a potential biomarker of Alzheimer’s disease. Mol Neurobiol 56:5792–5798. https://doi.org/10.1007/s12035-019-1501-xCrossRefPubMed

Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E (2011) Alzheimer’s disease. Lancet 377:1019–1031. https://doi.org/10.1016/S0140-6736(10)61349-9CrossRefPubMed

Barthelemy NR, Bateman RJ, Hirtz C, Marin P, Becher F, Sato C, Gabelle A, Lehmann S (2020) Cerebrospinal fluid phospho-tau T217 outperforms T181 as a biomarker for the differential diagnosis of Alzheimer’s disease and PET amyloid-positive patient identification. Alzheimers Res Ther 12:26. https://doi.org/10.1186/s13195-020-00596-4CrossRefPubMedPubMedCentral

Barthelemy NR, Horie K, Sato C, Bateman RJ (2020) Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease. J Exp Med. https://doi.org/10.1084/jem.20200861CrossRefPubMedPubMedCentral

Botha J, Pugsley HR, Handberg A (2021) Conventional, high-resolution and imaging flow cytometry: benchmarking performance in characterisation of extracellular vesicles. Biomedicines. https://doi.org/10.3390/biomedicines9020124CrossRefPubMedPubMedCentral

Clark CM, Pontecorvo MJ, Beach TG, Bedell BJ, Coleman RE, Doraiswamy PM, Fleisher AS, Reiman EM, Sabbagh MN, Sadowsky CH et al (2012) Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 11:669–678. https://doi.org/10.1016/S1474-4422(12)70142-4CrossRefPubMed

Delgado C, Bu L, Zhang J, Liu FY, Sall J, Liang FX, Furley AJ, Fishman GI (2021) Neural cell adhesion molecule is required for ventricular conduction system development. Development. https://doi.org/10.1242/dev.199431CrossRefPubMedPubMedCentral

Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y et al (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366:2112–2117. https://doi.org/10.1016/S0140-6736(05)67889-0CrossRefPubMedPubMedCentral

Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, Abner EL, Petersen RC, Federoff HJ, Miller BL et al (2015) Identification of preclinical Alzheimer’s disease by a profile of pathogenic proteins in neurally derived blood exosomes: a case–control study. Alzheimers Dement 11(600–607):e601. https://doi.org/10.1016/j.jalz.2014.06.008CrossRef

10.

Ganesh K, Basnet H, Kaygusuz Y, Laughney AM, He L, Sharma R, O’Rourke KP, Reuter VP, Huang YH, Turkekul M et al (2020) L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer. Nat Cancer 1:28–45. https://doi.org/10.1038/s43018-019-0006-xCrossRefPubMedPubMedCentral

11.

Giordano M, Decio A, Battistini C, Baronio M, Bianchi F, Villa A, Bertalot G, Freddi S, Lupia M, Jodice MG et al (2021) L1CAM promotes ovarian cancer stemness and tumor initiation via FGFR1/SRC/STAT3 signaling. J Exp Clin Cancer Res 40:319. https://doi.org/10.1186/s13046-021-02117-zCrossRefPubMedPubMedCentral

12.

Goetzl EJ, Abner EL, Jicha GA, Kapogiannis D, Schwartz JB (2018) Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer’s disease. FASEB J 32:888–893. https://doi.org/10.1096/fj.201700731RCrossRefPubMed

13.

Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL, Jicha GA, Karydas AM, Boxer A, Miller BL (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.201600816RCrossRefPubMedPubMedCentral

14.

Goetzl EJ, Mustapic M, Kapogiannis D, Eitan E, Lobach IV, Goetzl L, Schwartz JB, Miller BL (2016) Cargo proteins of plasma astrocyte-derived exosomes in Alzheimer’s disease. FASEB J 30:3853–3859. https://doi.org/10.1096/fj.201600756RCrossRefPubMedPubMedCentral

15.

Goetzl EJ, Peltz CB, Mustapic M, Kapogiannis D, Yaffe K (2020) Neuron-derived plasma exosome proteins after remote traumatic brain injury. J Neurotrauma 37:382–388. https://doi.org/10.1089/neu.2019.6711CrossRefPubMed

16.

Hansson O (2021) Biomarkers for neurodegenerative diseases. Nat Med 27:954–963. https://doi.org/10.1038/s41591-021-01382-xCrossRefPubMed

17.

Hansson O, Seibyl J, Stomrud E, Zetterberg H, Trojanowski JQ, Bittner T, Lifke V, Corradini V, Eichenlaub U, Batrla R et al (2018) CSF biomarkers of Alzheimer’s disease concord with amyloid-beta PET and predict clinical progression: a study of fully automated immunoassays in BioFINDER and ADNI cohorts. Alzheimers Dement 14:1470–1481. https://doi.org/10.1016/j.jalz.2018.01.010CrossRefPubMedPubMedCentral

18.

Henriksen K, O’Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A, Blennow K, Lonneborg A, Wyss-Coray T, Soares H 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.2013.01.013CrossRefPubMed

19.

Hong Z, Tian C, Stewart T, Aro P, Soltys D, Bercow M, Sheng L, Borden K, Khrisat T, Pan C et al (2021) Development of a sensitive diagnostic assay for parkinson disease quantifying alpha-synuclein-containing extracellular vesicles. Neurology 96:e2332–e2345. https://doi.org/10.1212/WNL.0000000000011853CrossRefPubMedPubMedCentral

20.

Hwang H, Zhang J, Chung KA, Leverenz JB, Zabetian CP, Peskind ER, Jankovic J, Su Z, Hancock AM, Pan C et al (2010) Glycoproteomics in neurodegenerative diseases. Mass Spectrom Rev 29:79–125. https://doi.org/10.1002/mas.20221ADSCrossRefPubMedPubMedCentral

21.

Ichikawa T, Okugawa Y, Toiyama Y, Tanaka K, Yin C, Kitajima T, Kondo S, Shimura T, Ohi M, Araki T et al (2019) Clinical significance and biological role of L1 cell adhesion molecule in gastric cancer. Br J Cancer 121:1058–1068. https://doi.org/10.1038/s41416-019-0646-8CrossRefPubMedPubMedCentral

22.

Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J et al (2018) NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement 14:535–562. https://doi.org/10.1016/j.jalz.2018.02.018CrossRefPubMedPubMedCentral

23.

Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O, van Westen D, Stomrud E, Minthon L, Blennow K et al (2016) CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol 3:154–165. https://doi.org/10.1002/acn3.274CrossRefPubMedPubMedCentral

24.

Jia L, Qiu Q, Zhang H, Chu L, Du Y, Zhang J, Zhou C, Liang F, Shi S, Wang S et al (2019) Concordance between the assessment of Abeta42, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid. Alzheimers Dement 15:1071–1080. https://doi.org/10.1016/j.jalz.2019.05.002CrossRefPubMed

25.

Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, Chamoun M, Savard M, Kang MS, Therriault J et al (2020) Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol 19:422–433. https://doi.org/10.1016/S1474-4422(20)30071-5CrossRefPubMed

26.

Kumar A, Su Y, Sharma M, Singh S, Kim S, Peavey JJ, Suerken CK, Lockhart SN, Whitlow CT, Craft S et al (2023) MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer’s disease. Alzheimers Dement 19:4952–4966. https://doi.org/10.1002/alz.13055CrossRefPubMed

27.

Lo TW, Figueroa-Romero C, Hur J, Pacut C, Stoll E, Spring C, Lewis R, Nair A, Goutman SA, Sakowski SA et al (2021) Extracellular vesicles in serum and central nervous system tissues contain microRNA signatures in sporadic amyotrophic lateral sclerosis. Front Mol Neurosci 14:739016. https://doi.org/10.3389/fnmol.2021.739016CrossRefPubMedPubMedCentral

28.

Manolopoulos A, Delgado-Peraza F, Mustapic M, Pucha KA, Nogueras-Ortiz C, Daskalopoulos A, Knight DD, Leoutsakos JM, Oh ES, Lyketsos CG et al (2023) Comparative assessment of Alzheimer’s disease-related biomarkers in plasma and neuron-derived extracellular vesicles: a nested case-control study. Front Mol Biosci 10:1254834. https://doi.org/10.3389/fmolb.2023.1254834CrossRefPubMedPubMedCentral

29.

Mattsson-Carlgren N, Andersson E, Janelidze S, Ossenkoppele R, Insel P, Strandberg O, Zetterberg H, Rosen HJ, Rabinovici G, Chai X et al (2020) Abeta deposition is associated with increases in soluble and phosphorylated tau that precede a positive Tau PET in Alzheimer’s disease. Sci Adv 6:eaaz2387. https://doi.org/10.1126/sciadv.aaz2387ADSCrossRefPubMedPubMedCentral

30.

Mattsson-Carlgren N, Janelidze S, Palmqvist S, Cullen N, Svenningsson AL, Strandberg O, Mengel D, Walsh DM, Stomrud E, Dage JL et al (2020) Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease. Brain 143:3234–3241. https://doi.org/10.1093/brain/awaa286CrossRefPubMedPubMedCentral

31.

Mattsson-Carlgren N, Leuzy A, Janelidze S, Palmqvist S, Stomrud E, Strandberg O, Smith R, Hansson O (2020) The implications of different approaches to define AT(N) in Alzheimer disease. Neurology 94:e2233–e2244. https://doi.org/10.1212/WNL.0000000000009485CrossRefPubMedPubMedCentral

32.

Mielke MM, Dage JL, Frank RD, Algeciras-Schimnich A, Knopman DS, Lowe VJ, Bu G, Vemuri P, Graff-Radford J, Jack CR et al (2022) Performance of plasma phosphorylated tau 181 and 217 in the community. Nat Med 28:1398–1405. https://doi.org/10.1038/s41591-022-01822-2CrossRefPubMedPubMedCentral

33.

Mielke MM, Frank RD, Dage JL, Jeromin A, Ashton NJ, Blennow K, Karikari TK, Vanmechelen E, Zetterberg H, Algeciras-Schimnich A et al (2021) Comparison of plasma phosphorylated Tau species with amyloid and Tau positron emission tomography, neurodegeneration, vascular pathology, and cognitive outcomes. JAMA Neurol 78:1108–1117. https://doi.org/10.1001/jamaneurol.2021.2293CrossRefPubMed

34.

Norman M, Ter-Ovanesyan D, Trieu W, Lazarovits R, Kowal EJK, Lee JH, Chen-Plotkin AS, Regev A, Church GM, Walt DR (2021) L1CAM is not associated with extracellular vesicles in human cerebrospinal fluid or plasma. Nat Methods 18:631–634. https://doi.org/10.1038/s41592-021-01174-8CrossRefPubMedPubMedCentral

35.

Palmqvist S, Janelidze S, Quiroz YT, Zetterberg H, Lopera F, Stomrud E, Su Y, Chen Y, Serrano GE, Leuzy A et al (2020) Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA 324:772–781. https://doi.org/10.1001/jama.2020.12134CrossRefPubMed

36.

Palmqvist S, Zetterberg H, Blennow K, Vestberg S, Andreasson U, Brooks DJ, Owenius R, Hagerstrom D, Wollmer P, Minthon L et al (2014) 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 71:1282–1289. https://doi.org/10.1001/jamaneurol.2014.1358CrossRefPubMed

37.

Preische O, Schultz SA, Apel A, Kuhle J, Kaeser SA, Barro C, Graber S, Kuder-Buletta E, LaFougere C, Laske C et al (2019) Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease. Nat Med 25:277–283. https://doi.org/10.1038/s41591-018-0304-3CrossRefPubMedPubMedCentral

38.

Russell AE, Sneider A, Witwer KW, Bergese P, Bhattacharyya SN, Cocks A, Cocucci E, Erdbrugger U, Falcon-Perez JM, Freeman DW et al (2019) Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop. J Extracell Vesicles 8:1684862. https://doi.org/10.1080/20013078.2019.1684862CrossRefPubMedPubMedCentral

39.

Sabri O, Sabbagh MN, Seibyl J, Barthel H, Akatsu H, Ouchi Y, Senda K, Murayama S, Ishii K, Takao M et al (2015) Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer’s disease: phase 3 study. Alzheimers Dement 11:964–974. https://doi.org/10.1016/j.jalz.2015.02.004CrossRefPubMed

40.

Shi M, Bradner J, Hancock AM, Chung KA, Quinn JF, Peskind ER, Galasko D, Jankovic J, Zabetian CP, Kim HM et al (2011) Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol 69:570–580. https://doi.org/10.1002/ana.22311CrossRefPubMedPubMedCentral

41.

Shi M, Kovac A, Korff A, Cook TJ, Ginghina C, Bullock KM, Yang L, Stewart T, Zheng D, Aro P et al (2016) CNS tau efflux via exosomes is likely increased in Parkinson’s disease but not in Alzheimer’s disease. Alzheimers Dement 12:1125–1131. https://doi.org/10.1016/j.jalz.2016.04.003CrossRefPubMedPubMedCentral

42.

Shi M, Liu C, Cook TJ, Bullock KM, Zhao Y, Ginghina C, Li Y, Aro P, Dator R, He C et al (2014) Plasma exosomal alpha-synuclein is likely CNS-derived and increased in Parkinson’s disease. Acta Neuropathol 128:639–650. https://doi.org/10.1007/s00401-014-1314-yCrossRefPubMedPubMedCentral

43.

Shi M, Zabetian CP, Hancock AM, Ginghina C, Hong Z, Yearout D, Chung KA, Quinn JF, Peskind ER, Galasko 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.2010.06.009CrossRefPubMedPubMedCentral

44.

Simren J, Leuzy A, Karikari TK, Hye A, Benedet AL, Lantero-Rodriguez J, Mattsson-Carlgren N, Scholl M, Mecocci P, Vellas B et al (2021) The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer’s disease. Alzheimers Dement 17:1145–1156. https://doi.org/10.1002/alz.12283CrossRefPubMedPubMedCentral

45.

Skog MS, Nystedt J, Korhonen M, Anderson H, Lehti TA, Pajunen MI, Finne J (2016) Expression of neural cell adhesion molecule and polysialic acid in human bone marrow-derived mesenchymal stromal cells. Stem Cell Res Ther 7:113. https://doi.org/10.1186/s13287-016-0373-5CrossRefPubMedPubMedCentral

46.

Somplatzki S, Muhlenhoff M, Kroger A, Gerardy-Schahn R, Boldicke T (2017) Intrabodies against the polysialyltransferases ST8SiaII and ST8SiaIV inhibit polysialylation of NCAM in rhabdomyosarcoma tumor cells. BMC Biotechnol 17:42. https://doi.org/10.1186/s12896-017-0360-7CrossRefPubMedPubMedCentral

47.

Sun R, Wang H, Shi Y, Sun Z, Jiang H, Zhang J (2020) Changes in the morphology, number, and pathological protein levels of plasma exosomes may help diagnose Alzheimer’s disease. J Alzheimers Dis 73:909–917. https://doi.org/10.3233/JAD-190497CrossRefPubMed

48.

Thery C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK et al (2018) Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles 7:1535750. https://doi.org/10.1080/20013078.2018.1535750CrossRefPubMedPubMedCentral

49.

Thijssen EH, La Joie R, Wolf A, Strom A, Wang P, Iaccarino L, Bourakova V, Cobigo Y, Heuer H, Spina S et al (2020) Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nat Med 26:387–397. https://doi.org/10.1038/s41591-020-0762-2CrossRefPubMedPubMedCentral

50.

Tian C, Stewart T, Hong Z, Guo Z, Aro P, Soltys D, Pan C, Peskind ER, Zabetian CP, Shaw LM et al (2022) Blood extracellular vesicles carrying synaptic function- and brain-related proteins as potential biomarkers for Alzheimer’s disease. Alzheimers Dement. https://doi.org/10.1002/alz.12723CrossRefPubMedPubMedCentral

51.

Tian Y, Gong M, Hu Y, Liu H, Zhang W, Zhang M, Hu X, Aubert D, Zhu S, Wu L et al (2020) Quality and efficiency assessment of six extracellular vesicle isolation methods by nano-flow cytometry. J Extracell Vesicles 9:1697028. https://doi.org/10.1080/20013078.2019.1697028CrossRefPubMed

52.

Tian Y, Ma L, Gong M, Su G, Zhu S, Zhang W, Wang S, Li Z, Chen C, Li L et al (2018) Protein profiling and sizing of extracellular vesicles from colorectal cancer patients via flow cytometry. ACS Nano 12:671–680. https://doi.org/10.1021/acsnano.7b07782CrossRefPubMed

53.

Urbanelli L, Buratta S, Sagini K, Tancini B, Emiliani C (2016) Extracellular vesicles as new players in cellular senescence. Int J Mol Sci 17:66. https://doi.org/10.3390/ijms17091408CrossRef

54.

van der Pol E, de Rond L, Coumans FAW, Gool EL, Boing AN, Sturk A, Nieuwland R, van Leeuwen TG (2018) Absolute sizing and label-free identification of extracellular vesicles by flow cytometry. Nanomedicine 14:801–810. https://doi.org/10.1016/j.nano.2017.12.012CrossRefPubMed

55.

Weller J, Budson A (2018) Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res. https://doi.org/10.12688/f1000research.14506.1CrossRefPubMedPubMedCentral

56.

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

57.

Xu J, Ma H, Liu Y (2017) Stochastic Optical Reconstruction Microscopy (STORM). Curr Protoc Cytom 81:124611–124627. https://doi.org/10.1002/cpcy.23

58.

Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, Wilson B, Zhang W, Zhou Y, Hong JS et al (2005) Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J 19:533–542. https://doi.org/10.1096/fj.04-2751comCrossRefPubMed

59.

Zhong Z, Rosenow M, Xiao N, Spetzler D (2018) Profiling plasma extracellular vesicle by pluronic block-copolymer based enrichment method unveils features associated with breast cancer aggression, metastasis and invasion. J Extracell Vesicles 7:1458574. https://doi.org/10.1080/20013078.2018.1458574CrossRefPubMedPubMedCentral

Title: Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis
Authors: Zhen Guo
Chen Tian
Yang Shi
Xue-Ru Song
Wei Yin
Qing-Qing Tao
Jie Liu
Guo-Ping Peng
Zhi-Ying Wu
Yan-Jiang Wang
Zhen-Xin Zhang
Jing Zhang
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Alzheimer's Disease
Alzheimer's Disease
Biomarkers
Dementia
Dementia
Published in: Acta Neuropathologica Communications / Issue 1/2024
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-024-01727-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer’s disease diagnosis and differential diagnosis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2024

Neuropathological changes associated with aberrant cerebrospinal fluid p-tau181 and Aβ42 in Alzheimer’s disease and other neurodegenerative diseases

The cycad genotoxin methylazoxymethanol, linked to Guam ALS/PDC, induces transcriptional mutagenesis

Mouse serum albumin induces neuronal apoptosis and tauopathies

Correction to: Mild traumatic brain injury induces microvascular injury and accelerates Alzheimer-like pathogenesis in mice

Decoding of the surfaceome and endocytome in primary glioblastoma cells identifies potential target antigens in the hypoxic tumor niche

Correction: Lesion of the subiculum reduces the spread of amyloid beta pathology to interconnected brain regions in a mouse model of Alzheimer’s disease