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

Massimo S. Fiandaca, Dimitrios Kapogiannis, Mark Mapstone, Adam Boxer, Erez Eitan, Janice B. Schwartz, Erin L. Abner, Ronald Carl Petersen, Howard J. Federoff, Bruce L. Miller, Edward J. Goetzl

Research output: Contribution to journalArticle

236 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)600-607.e1
JournalAlzheimer's and Dementia
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2015

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Exosomes
Case-Control Studies
Alzheimer Disease
Frontotemporal Dementia
Amyloid
Proteins
Biomarkers

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 journalArticle

Fiandaca, MS, Kapogiannis, D, Mapstone, M, Boxer, A, Eitan, E, Schwartz, JB, Abner, EL, Petersen, RC, Federoff, HJ, Miller, BL & Goetzl, EJ 2015, 'Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study', Alzheimer's and Dementia, vol. 11, no. 6, pp. 600-607.e1. https://doi.org/10.1016/j.jalz.2014.06.008
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. / Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes : A case-control study. In: Alzheimer's and Dementia. 2015 ; Vol. 11, No. 6. pp. 600-607.e1.
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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.",
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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

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