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

INSIGHT-preAD Study Group, Alzheimer Precision Medicine Initiative (APMI)

Research output: Contribution to journalArticle

12 Scopus citations


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 languageEnglish
Pages (from-to)1623-1631
Number of pages9
JournalAlzheimer's and Dementia
Issue number12
StatePublished - Dec 2018



  • Alzheimer's disease
  • Amyloid PET
  • Cerebrospinal fluid
  • Monocentric
  • Preclinical
  • SUVR
  • Subjective memory complainers
  • Synergistic
  • Tau protein
  • α-Synuclein

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