α-Synuclein species as potential cerebrospinal fluid biomarkers for dementia with lewy bodies

Mov Disord. 2018 Nov;33(11):1724-1733. doi: 10.1002/mds.111. Epub 2018 Nov 15.

Abstract

Background: The objective of this study was to investigate the discriminating value of a range of CSF α-synuclein species for dementia with Lewy bodies compared with Alzheimer's disease, PD, and cognitively normal controls.

Methods: We applied our recently published enzyme-linked immunosorbent assays to measure the CSF levels of total α-synuclein, oligomeric α-synuclein, and phosphorylated α-synuclein in dementia with Lewy bodies (n = 42), Alzheimer's disease (n = 39), PD (n = 46), and controls (n = 78). General linear models corrected for age and sex were performed to assess differences in α-synuclein levels between groups. We used backward-elimination logistic regression analysis to investigate the combined discriminating value of the different CSF α-synuclein species and Alzheimer's disease biomarkers.

Results: CSF levels of total α-synuclein were lower in dementia with Lewy bodies and PD compared with Alzheimer's disease as well as controls (P < 0.001). In contrast, CSF levels of oligomeric α-synuclein were higher in dementia with Lewy bodies and PD compared with Alzheimer's disease (P < 0.05) and controls (P < 0.001). No group differences were found for phosphorylated α-synuclein. In dementia with Lewy bodies and PD, CSF total α-synuclein levels positively correlated with tau and phosphorylated tau (both r > 0.40, P < 0.01), but not with amyloid-β1-42 . The optimal combination to differentiate dementia with Lewy bodies from controls consisted of amyloid-β1-42 , tau, total α-synuclein, oligomeric α-synuclein, age, and sex (AUC, 0.90). To differentiate dementia with Lewy bodies from Alzheimer's disease, the combination of tau and oligomeric α-synuclein resulted in an AUC of 0.83. CSF α-synuclein species do not contribute to the differentiation of dementia with Lewy bodies from PD.

Conclusions: CSF α-synuclein species could be useful as part of a biomarker panel for dementia with Lewy bodies. Evaluating both oligomeric α-synuclein and total α-synuclein in CSF helps in the diagnosis of dementia with Lewy bodies. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Keywords: CSF; biomarkers; dementia with Lewy bodies; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnostic imaging
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid*
  • Electroencephalography
  • Female
  • Humans
  • Lewy Body Disease / cerebrospinal fluid*
  • Lewy Body Disease / diagnostic imaging
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease / cerebrospinal fluid
  • Parkinson Disease / diagnostic imaging
  • Peptide Fragments / cerebrospinal fluid
  • Psychiatric Status Rating Scales
  • Retrospective Studies
  • Tomography, Emission-Computed, Single-Photon
  • Tropanes / pharmacokinetics
  • alpha-Synuclein / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • Tropanes
  • alpha-Synuclein
  • amyloid beta-protein (1-42)
  • tau Proteins
  • 2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane