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

Alzheimers Dement. 2018 Dec;14(12):1623-1631. doi: 10.1016/j.jalz.2018.06.3053. Epub 2018 Jul 26.


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.

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

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Amyloid / metabolism*
  • Apolipoprotein E4 / genetics
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Cognition
  • Cohort Studies
  • Cross-Sectional Studies
  • Diagnostic Self Evaluation
  • Female
  • Humans
  • Male
  • Memory Disorders / diagnosis*
  • Positron-Emission Tomography
  • Prodromal Symptoms
  • alpha-Synuclein / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*


  • Amyloid
  • Apolipoprotein E4
  • Biomarkers
  • MAPT protein, human
  • SNCA protein, human
  • alpha-Synuclein
  • tau Proteins