Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

INSIGHT-preAD Study Group, Alzheimer Precision Medicine Initiative (APMI)

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Introduction: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results: We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. Discussion: Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.

Original languageEnglish
Pages (from-to)1623-1631
Number of pages9
JournalAlzheimer's and Dementia
Volume14
Issue number12
DOIs
StatePublished - 1 Dec 2018

Fingerprint

Synucleins
Amyloid
Cerebrospinal Fluid
Alzheimer Disease
Biomarkers
Brain
Proteins
Neurodegenerative Diseases
Observational Studies
Animal Models

Keywords

  • Alzheimer's disease
  • Amyloid PET
  • Cerebrospinal fluid
  • Monocentric
  • Preclinical
  • SUVR
  • Subjective memory complainers
  • Synergistic
  • Tau protein
  • α-Synuclein

Cite this

@article{18bed86728e34a7fb96860960f0a19d6,
title = "Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers",
abstract = "Introduction: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results: We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. Discussion: Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.",
keywords = "Alzheimer's disease, Amyloid PET, Cerebrospinal fluid, Monocentric, Preclinical, SUVR, Subjective memory complainers, Synergistic, Tau protein, α-Synuclein",
author = "{INSIGHT-preAD Study Group} and {Alzheimer Precision Medicine Initiative (APMI)} and Andrea Vergallo and Bun, {Ren{\'e} Sosata} and Nicola Toschi and Filippo Baldacci and Henrik Zetterberg and Kaj Blennow and Enrica Cavedo and Foudil Lamari and Habert, {Marie Odile} and Bruno Dubois and Roberto Floris and Francesco Garaci and Simone Lista and Harald Hampel and C. Audrain and A. Auffret and H. Bakardjian and F. Baldacci and B. Batrancourt and I. Benakki and H. Benali and H. Bertin and A. Bertrand and L. Boukadida and F. Cacciamani and V. Causse and E. Cavedo and {Cherif Touil}, S. and Chiesa, {P. A.} and O. Colliot and {Dalla Barba}, G. and M. Depaulis and {Dos Santos}, A. and B. Dubois and M. Dubois and S. Epelbaum and B. Fontaine and H. Francisque and G. Gagliardi and A. Genin and R. Genthon and P. Glasman and F. Gombert and Habert, {M. O.} and H. Hampel and H. Hewa and M. Houot and N. Jungalee and A. Kas and Sidney O'Bryant",
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Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers. / INSIGHT-preAD Study Group; Alzheimer Precision Medicine Initiative (APMI).

In: Alzheimer's and Dementia, Vol. 14, No. 12, 01.12.2018, p. 1623-1631.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of cerebrospinal fluid α-synuclein with total and phospho-tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers

AU - INSIGHT-preAD Study Group

AU - Alzheimer Precision Medicine Initiative (APMI)

AU - Vergallo, Andrea

AU - Bun, René Sosata

AU - Toschi, Nicola

AU - Baldacci, Filippo

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Cavedo, Enrica

AU - Lamari, Foudil

AU - Habert, Marie Odile

AU - Dubois, Bruno

AU - Floris, Roberto

AU - Garaci, Francesco

AU - Lista, Simone

AU - Hampel, Harald

AU - Audrain, C.

AU - Auffret, A.

AU - Bakardjian, H.

AU - Baldacci, F.

AU - Batrancourt, B.

AU - Benakki, I.

AU - Benali, H.

AU - Bertin, H.

AU - Bertrand, A.

AU - Boukadida, L.

AU - Cacciamani, F.

AU - Causse, V.

AU - Cavedo, E.

AU - Cherif Touil, S.

AU - Chiesa, P. A.

AU - Colliot, O.

AU - Dalla Barba, G.

AU - Depaulis, M.

AU - Dos Santos, A.

AU - Dubois, B.

AU - Dubois, M.

AU - Epelbaum, S.

AU - Fontaine, B.

AU - Francisque, H.

AU - Gagliardi, G.

AU - Genin, A.

AU - Genthon, R.

AU - Glasman, P.

AU - Gombert, F.

AU - Habert, M. O.

AU - Hampel, H.

AU - Hewa, H.

AU - Houot, M.

AU - Jungalee, N.

AU - Kas, A.

AU - O'Bryant, Sidney

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Introduction: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results: We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. Discussion: Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.

AB - Introduction: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α-synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α-synuclein (α-syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods: The pathophysiological role of CSF α-syn in asymptomatic subjects at risk of AD has not been explored. We performed a large-scale cross-sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT-preAD). Results: We found a positive association between CSF α-syn concentrations and brain β-amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α-syn and both CSF t-tau and p-tau181 concentrations. Discussion: Animal models presented evidence, indicating that α-syn may synergistically and directly induce fibrillization of both tau and β-amyloid. Our data indicate an association of CSF α-syn with AD-related pathophysiological mechanisms, during the preclinical phase of the disease.

KW - Alzheimer's disease

KW - Amyloid PET

KW - Cerebrospinal fluid

KW - Monocentric

KW - Preclinical

KW - SUVR

KW - Subjective memory complainers

KW - Synergistic

KW - Tau protein

KW - α-Synuclein

UR - http://www.scopus.com/inward/record.url?scp=85054461082&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2018.06.3053

DO - 10.1016/j.jalz.2018.06.3053

M3 - Article

C2 - 30055132

AN - SCOPUS:85054461082

VL - 14

SP - 1623

EP - 1631

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 12

ER -