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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 600-607.e1 |
| Journal | Alzheimer's and Dementia |
| Volume | 11 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2015 |
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Keywords
- Aβ1-42
- Biomarkers
- Neural exosomes
- P-Tau
- Preclinical AD
ASJC Scopus subject areas
- Clinical Neurology
- Developmental Neuroscience
- Cellular and Molecular Neuroscience
- Psychiatry and Mental health
- Geriatrics and Gerontology
- Epidemiology
- Health Policy
Cite this
Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes : A case-control study. / Fiandaca, Massimo S.; Kapogiannis, Dimitrios; Mapstone, Mark; Boxer, Adam; Eitan, Erez; Schwartz, Janice B.; Abner, Erin L.; Petersen, Ronald Carl; Federoff, Howard J.; Miller, Bruce L.; Goetzl, Edward J.
In: Alzheimer's and Dementia, Vol. 11, No. 6, 01.06.2015, p. 600-607.e1.Research output: Contribution to journal › Article
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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 Carl
AU - Federoff, Howard J.
AU - Miller, Bruce L.
AU - Goetzl, Edward J.
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
VL - 11
SP - 600-607.e1
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 6
ER -