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