期刊
ALZHEIMERS & DEMENTIA
卷 11, 期 6, 页码 600-607出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2014.06.008
关键词
Preclinical AD; Neural exosomes; P-Tau; A beta 1-42; Biomarkers
资金
- Intramural Research Program of the National Institute on Aging (NIA)
- NIA from the National Institutes of Health (NIH) [RO1AG030753]
- UK ADC [P30 AG028383]
- Nanosomix, Inc.
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 beta 1-42 (A beta 1-42) for AD and levels of P-T181-tau and A beta 1-42 for FTD were significantly higher than for case-controls. Step-wise discriminant modeling incorporated P-T181-tau, P-S396-tau, and A beta 1-42 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 A beta 1-42 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 A beta 1-42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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