Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease

Neurology. 2010 Nov 16;75(20):1766-72. doi: 10.1212/WNL.0b013e3181fd613b. Epub 2010 Oct 20.


Background: To date, there is no accepted clinical diagnostic test for Parkinson disease (PD) that is based on biochemical analysis of blood or CSF. The discovery of mutations in the SNCA gene encoding α-synuclein in familial parkinsonism and the accumulation of α-synuclein in the PD brain suggested a critical role for this protein in PD etiology.

Methods: We investigated total and α-synuclein oligomers levels in CSF from patients clinically diagnosed with PD, progressive supranuclear palsy (PSP), or Alzheimer disease (AD), and age-matched controls, using ELISA developed in our laboratory.

Results: The levels of α-synuclein oligomers and oligomers/total-α-synuclein ratio in CSF were higher in the PD group (n = 32; p < 0.0001, Mann-Whitney U test) compared to the control group (n = 28). The area under the receiver operating characteristic curve (AUC) indicated a sensitivity of 75.0% and a specificity of 87.5%, with an AUC of 0.859 for increased CSF α-synuclein oligomers in clinically diagnosed PD cases. However, when the CSF oligomers/total-α-synuclein ratio was analyzed, it provided an even greater sensitivity of 89.3% and specificity of 90.6%, with an AUC of 0.948. In another cross-sectional pilot study, we confirmed that the levels of CSF α-synuclein oligomers were higher in patients with PD (n = 25) compared to patients with PSP (n = 18; p < 0.05) or AD (n = 35; p < 0.001) or control subjects (n = 43; p < 0.05).

Conclusion: Our results demonstrate that levels of α-synuclein oligomers in CSF and the oligomers/total-α-synuclein ratio can be useful biomarkers for diagnosis and early detection of PD.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / metabolism
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / chemistry
  • Brain Chemistry
  • Cohort Studies
  • Cross-Sectional Studies / methods
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / cerebrospinal fluid*
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / metabolism
  • Pilot Projects
  • Supranuclear Palsy, Progressive / cerebrospinal fluid
  • Supranuclear Palsy, Progressive / diagnosis
  • Supranuclear Palsy, Progressive / metabolism
  • Up-Regulation / physiology
  • alpha-Synuclein / cerebrospinal fluid*
  • alpha-Synuclein / chemistry


  • Biomarkers
  • alpha-Synuclein