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
Year: 2018
Type: article
Study design: Observational Study
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.
Source: Alzheimer s & Dementia
Authors: Andrea Vergallo, René‐Sosata Bun, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Enrica Cavedo, Foudil Lamari, Marie‐Odile Habert, Bruno Dubois, Roberto Floris, Francesco Garaci, Simone Lista, Harald Hampel, INSIGHT‐preAD study group, for the lzheimer Precision Medicine Initiative (APMI)
Institutions: Centre National de la Recherche Scientifique, Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, AXA Research Fund, Institut du Cerveau, Alzheimer Precision Medicine, University of Rome Tor Vergata, Harvard University, Athinoula A. Martinos Center for Biomedical Imaging, University of Pisa, Sahlgrenska University Hospital, UK Dementia Research Institute, National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, Centro San Giovanni di Dio Fatebenefratelli, Laboratoire d’Imagerie Biomédicale, Centre d'Acquisition et de Traitement des Images, Università degli studi di Cassino e del Lazio Meridionale
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Funders: Eli Lilly and Company, Pfizer, Rotary Foundation, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, AXA Research Fund, Centre Hospitalier Universitaire de Bordeaux, Sorbonne Université, Fondation pour la Recherche sur Alzheimer, Medical Research Council
OpenAlex ID: W2883052156