@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 = "{Alzheimer Precision Medicine Initiative (APMI)} and {INSIGHT-preAD Study Group} 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 B. Batrancourt and I. Benakki and H. Benali and H. Bertin and A. Bertrand and L. Boukadida and F. Cacciamani and V. Causse and {Cherif Touil}, S. and Chiesa, {P. A.} and O. Colliot and {Dalla Barba}, G. and M. Depaulis and {Dos Santos}, A. 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 H. Hewa and M. Houot and N. Jungalee and A. Kas and M. Kilani and {La Corte}, V. and {Le Roy}, F. and S. Lehericy and C. Letondor and O'Bryant, {S. E.}",
note = "Funding Information: The study was promoted by INSERM in collaboration with ICM, IHU-A-ICM, and Pfizer and has received a support within the ?Investissement d'Avenir? (ANR-10-AIHU-06). The study was promoted in collaboration with the ?CHU de Bordeaux? (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly. A.V. is supported by Rotary Club Livorno ?Mascagni?/the Rotary Foundation (Global Grant No GG1758249). H.Z. is a Wallenberg Academy Fellow and holds grants from the Swedish and European Research Councils as well as the Medical Research Council (UK). K.B. holds the Torsten S?derberg Professorship of Medicine. H.H. is supported by the AXA Research Fund, the ?Fondation partenariale Sorbonne Universit?? and the ?Fondation pour la Recherche sur Alzheimer? Paris, France. Ce travail a b?n?fici? d'une aide de l'Etat ?Investissements d'avenir? ANR-10-IAIHU-06. The research leading to these results has received funding from the program ?Investissements d'avenir? ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6). This research benefited from the support of the Program ?PHOENIX? led by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer. Contributors to the Alzheimer Precision Medicine Initiative Working Group (APMI?WG): Aguilar LF (Montr?al), Babiloni C (Rome), Baldacci F (Pisa), Benda N (Bonn), Black KL (Los Angeles), Bokde ALW (Dublin), Bonuccelli U (Pisa), Broich K (Bonn), Bun RS (Paris), Cacciola F (Siena), Castrillo J ? (Derio), Cavedo E (Paris), Ceravolo R (Pisa), Chiesa PA (Paris), Colliot O (Paris), Coman CM (Paris), Corvol JC (Paris), Cuello AC (Montr?al), Cummings JL (Las Vegas), Depypere H (Gent), Dubois B (Paris), Duggento A (Rome), Durrleman S (Paris), Escott-Price V (Cardiff), Federoff H (Irvine), Ferretti MT (Z?rich), Fiandaca M (Irvine), Frank RA (Malvern), Garaci F (Rome), Genthon R (Paris), George N (Paris), Giorgi FS (Pisa), Graziani M (Roma), Haberkamp M (Bonn), Habert MO (Paris), Hampel H (Paris), Herholz K (Manchester), Karran E (Cambridge), Kim SH (Seoul), Koronyo Y (Los Angeles), Koronyo-Hamaoui M (Los Angeles), Lamari F (Paris), Langevin T (Minneapolis-Saint Paul), Leh?ricy S (Paris), Lista S (Paris), Lorenceau J (Paris), Mapstone M (Irvine), Neri C (Paris), Nistic? R (Rome), Nyasse-Messene F (Paris), O'Bryant SE (Fort Worth), Perry G (San Antonio), Ritchie C (Edinburgh), Rojkova K (Paris), Rossi S (Siena), Santarnecchi E (Siena), Schneider LS (Los Angeles), Sporns O (Bloomington), Toschi N (Rome), Verdooner SR (Sacramento), Vergallo A (Paris), Villain N (Paris), Welikovitch L (Montr?al), Woodcock J (Silver Spring), Younesi E (Esch-sur-Alzette). INSIGHT-preAD Study Group: Audrain C, Auffret A, Bakardjian H, Baldacci F, Batrancourt B, Benakki I, Benali H, Bertin H, Bertrand A, Boukadida L, Cacciamani F, Causse V, Cavedo E, Cherif Touil S, Chiesa PA, Colliot O, Dalla Barba G, Depaulis M, Dos Santos A, Dubois B, Dubois M, Epelbaum S, Fontaine B, Francisque H, Gagliardi G, Genin A, Genthon R, Glasman P, Gombert F, Habert MO, Hampel H, Hewa H, Houot M, Jungalee N, Kas A, Kilani M, La Corte V, Le Roy F, Lehericy S, Letondor C, Levy M, Lista S, Lowrey M, Ly J, Makiese O, Masetti I, Mendes A, Metzinger C, Michon A, Mochel F, Nait Arab R, Nyasse F, Perrin C, Poirier F, Poisson C, Potier MC, Ratovohery S, Revillon M, Rojkova K, Santos-Andrade K, Schindler R, Servera MC, Seux L, Simon V, Skovronsky D, Thiebaut M, Uspenskaya O, Vlaincu M. INSIGHT-preAD Scientific Committee Members: Dubois B, Hampel H, Bakardjian H, Colliot O, Habert MO, Lamari F, Mochel F, Potier MC, Thiebaut de Schotten M. Funding Information: A.V. is supported by Rotary Club Livorno “Mascagni”/the Rotary Foundation (Global Grant No GG1758249). H.Z. is a Wallenberg Academy Fellow and holds grants from the Swedish and European Research Councils as well as the Medical Research Council (UK). K.B. holds the Torsten S{\"o}derberg Professorship of Medicine. H.H. is supported by the AXA Research Fund, the “Fondation partenariale Sorbonne Universit{\'e}” and the “Fondation pour la Recherche sur Alzheimer”, Paris, France. Ce travail a b{\'e}n{\'e}fici{\'e} d'une aide de l'Etat “Investissements d'avenir” ANR-10-IAIHU-06. The research leading to these results has received funding from the program “Investissements d'avenir” ANR-10-IAIHU-06 (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6). Funding Information: This research benefited from the support of the Program “PHOENIX” led by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer. Funding Information: The study was promoted by INSERM in collaboration with ICM, IHU-A-ICM, and Pfizer and has received a support within the “Investissement d'Avenir” (ANR-10-AIHU-06). The study was promoted in collaboration with the “CHU de Bordeaux” (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan-Alzheimer. The study was further supported by AVID/Lilly. Publisher Copyright: {\textcopyright} 2018 the Alzheimer's Association",
year = "2018",
month = dec,
doi = "10.1016/j.jalz.2018.06.3053",
language = "English",
volume = "14",
pages = "1623--1631",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "12",
}