Vergallo Andrea, Bun René-Sosata, Toschi Nicola, Baldacci Filippo, Zetterberg Henrik, Blennow Kaj, Cavedo Enrica, Lamari Foudil, Habert Marie-Odile, Dubois Bruno, Floris Roberto, Garaci Francesco, Lista Simone, Hampel Harald, 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., 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 M. O., 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 M. C., Ratovohery S., Revillon M., Rojkova K., Santos-Andrade K., Schindler R., Servera M. C., Seux L., Simon V., Skovronsky D., Thiebaut M., Uspenskaya O., Vlaincu M., Aguilar L. F.,
Babiloni C., Baldacci F., Benda N., Black K. L., Bokde A. L. W., Bonuccelli U., Broich K., Bun R. S., Cacciola F., Castrillo J., Cavedo E., Ceravolo R., Chiesa P. A., Colliot O., Coman C. M., Corvol J. C., Cuello A. C., Cummings J. L., Depypere H., Dubois B., Duggento A., Durrleman S., Escott-Price V., Federoff H., Ferretti M. T., Fiandaca M., Frank R. A., Garaci F., Genthon R., George N., Giorgi F. S.,
Graziani M., Haberkamp M., Habert M. O., Hampel H., Herholz K., Karran E., Kim S. H., Koronyo Y., Koronyo-Hamaoui M., Lamari F., Langevin T., Lehéricy S., Lista S., Lorenceau J., Mapstone M., Neri C., Nisticò R., Nyasse-Messene F., O'Bryant S. E., Perry G., Ritchie C., Rojkova K., Rossi S., Santarnecchi E., Schneider L. S., Sporns O., Toschi N., Verdooner S. R., Vergallo A., Villain N., Welikovitch L., Woodcock J., Younesi E.
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.
