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Alzheimers Dement. 2015 Jun;11(6):600-7.e1. doi: 10.1016/j.jalz.2014.06.008. Epub 2014 Aug 15.

Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study.

Author information

1
Departments of Neurology and Neuroscience, Georgetown University Medical Center, Washington, DC, USA.
2
Clinical Research Branch, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA.
3
Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
4
Department of Neurology, Memory and Aging Center, UCSF Medical Center, San Francisco, CA, USA.
5
Department of Medicine, UCSF Medical Center and the Jewish Home of San Francisco, San Francisco, CA, USA.
6
Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
7
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
8
Department of Medicine, UCSF Medical Center and the Jewish Home of San Francisco, San Francisco, CA, USA. Electronic address: edward.goetzl@ucsf.edu.

Abstract

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.

KEYWORDS:

Aβ1–42; Biomarkers; Neural exosomes; P-Tau; Preclinical AD

PMID:
25130657
PMCID:
PMC4329112
DOI:
10.1016/j.jalz.2014.06.008
[Indexed for MEDLINE]
Free PMC Article

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