Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study.
BACKGROUND
Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD.


METHODS
Blood exosomes obtained at one time-point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time-points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by enzyme-linked immunosorbent assays.


RESULTS
Mean exosomal levels of total tau, P-T181-tau, P-S396-tau, and amyloid β 1-42 (Aβ1-42) for AD and levels of P-T181-tau and Aβ1-42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and Aβ1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau, and Aβ1-42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD.


CONCLUSIONS
Levels of P-S396-tau, P-T181-tau, and Aβ1-42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset.
['Fiandaca|Massimo S|MS|', 'Kapogiannis|Dimitrios|D|', 'Mapstone|Mark|M|', 'Boxer|Adam|A|', 'Eitan|Erez|E|', 'Schwartz|Janice B|JB|', 'Abner|Erin L|EL|', 'Petersen|Ronald C|RC|', 'Federoff|Howard J|HJ|', 'Miller|Bruce L|BL|', 'Goetzl|Edward J|EJ|']
D000368:Aged D000369:Aged, 80 and over D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D015415:Biomarkers D016022:Case-Control Studies D003430:Cross-Sectional Studies D016002:Discriminant Analysis D004797:Enzyme-Linked Immunosorbent Assay D055354:Exosomes D005260:Female D057180:Frontotemporal Dementia D006801:Humans D008297:Male D008875:Middle Aged D010446:Peptide Fragments D010766:Phosphorylation D062706:Prodromal Symptoms D012189:Retrospective Studies D012720:Severity of Illness Index D013997:Time Factors D016875:tau Proteins
Biomarkers Aβ1–42 Neural exosomes P-Tau Preclinical AD