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).
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
UR - http://www.scopus.com/inward/record.url?scp=84931577633&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84931577633&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2014.06.008
DO - 10.1016/j.jalz.2014.06.008
M3 - Article
C2 - 25130657
AN - SCOPUS:84931577633
SN - 1552-5260
VL - 11
SP - 600-607.e1
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 6
ER -