TY - JOUR
T1 - Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes
T2 - A case-control study
AU - Fiandaca, Massimo S.
AU - Kapogiannis, Dimitrios
AU - Mapstone, Mark
AU - Boxer, Adam
AU - Eitan, Erez
AU - Schwartz, Janice B.
AU - Abner, Erin L.
AU - Petersen, Ronald C.
AU - Federoff, Howard J.
AU - Miller, Bruce L.
AU - Goetzl, Edward J.
N1 - Funding Information:
Funding: Intramural Research Program of the National Institute on Aging (NIA; DK, EE), NIA RO1AG030753 from the National Institutes of Health (NIH; HJF), UK ADC P30 AG028383 (ELA), and an unrestricted grant for technological development from Nanosomix, Inc. (EJG).
Funding Information:
Conflicts of interest: Only two authors report possible conflicts of interest. Dr. Boxer declares grants from NIH/NIA, grants from Tau Research Consortium, grants from Corticobasal Degeneration Solutions, grants, personal fees and non-financial support from Archer Biosciences, grants from Allon Therapeutics, personal fees from Acetylon, personal fees from Ipierian, grants from Genentech, grants from Bristol Myers Squibb, grants from TauRx, grants from Alzheimer's Association, grants from Bluefield Project to Cure FTD, grants from Association for Frontotemporal Degeneration, grants from Alzheimer's Drug Discovery Foundation, grants from EnVivo, grants from C2N Diagnostics, grants from Pfizer, grants from Eli Lilly, outside the submitted work. Dr. Goetzl has filed a provisional application with the U.S. Patent Office for the platform and methodologies described in this report. These data were presented in part by DK at the 2014 Alzheimer's Association International Conference in Copenhagen.
Publisher Copyright:
© 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - Aβ1-42
KW - Biomarkers
KW - Neural exosomes
KW - P-Tau
KW - Preclinical AD
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U2 - 10.1016/j.jalz.2014.06.008
DO - 10.1016/j.jalz.2014.06.008
M3 - Article
C2 - 25130657
AN - SCOPUS:84931577633
VL - 11
SP - 600-607.e1
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 6
ER -