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Association of cerebrospinal fluid α‐synuclein with total and phospho‐tau 181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers
Author(s) -
Vergallo Andrea,
Bun RenéSosata,
Toschi Nicola,
Baldacci Filippo,
Zetterberg Henrik,
Blennow Kaj,
Cavedo Enrica,
Lamari Foudil,
Habert MarieOdile,
Dubois Bruno,
Floris Roberto,
Garaci Francesco,
Lista Simone,
Hampel Harald
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.3053
Subject(s) - cerebrospinal fluid , asymptomatic , pathophysiology , disease , psychology , neuroscience , pathology , amyloid (mycology) , tau protein , alzheimer's disease , medicine
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‐tau 181 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.