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 language | English |
|---|---|
| Pages (from-to) | 1623-1631 |
| Number of pages | 9 |
| Journal | Alzheimer's and Dementia |
| Volume | 14 |
| Issue number | 12 |
| DOIs | |
| State | Published - 1 Dec 2018 |
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Keywords
- Alzheimer's disease
- Amyloid PET
- Cerebrospinal fluid
- Monocentric
- Preclinical
- SUVR
- Subjective memory complainers
- Synergistic
- Tau protein
- α-Synuclein
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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 journal › Article
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 -