Ratios of proteins in cerebrospinal fluid in Parkinson's disease cognitive decline: prospective study

Mov Disord. 2018 Nov;33(11):1809-1813. doi: 10.1002/mds.27518. Epub 2018 Nov 13.


Background: There is a need for biomarkers of dementia in PD.

Objectives: To determine if the levels of the main CSF proteins and their ratios are associated with deterioration in cognition and progression to dementia in the short to mid term.

Methods: The Parkinson's Progression Markers Initiative database was used as an exploratory cohort, and a center-based cohort was used as a replication cohort. Amyloid ß1-42, total tau, threonine-181 phosphorylated tau, and α-synuclein in the CSF and the ratios of these proteins were assessed.

Results: In the Parkinson's Progression Markers Initiative cohort (n = 281), the total tau/amyloid ß1-42, total tau/α-synuclein, total tau/amyloid ß1-42+α-synuclein, and amyloid ß1-42/total tau ratios were associated with a risk of progression to dementia over a 3-year follow-up. In the replication cohort (n = 40), the total tau/α-synuclein and total tau/amyloid ß1-42+α-synuclein ratios were associated with progression to dementia over a 41-month follow-up.

Conclusion: Ratios of the main proteins found in PD patient brain inclusions that can be measured in the CSF appear to have value as short- to mid-term predictors of dementia. © 2018 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; biomarkers; cerebrospinal fluid; dementia; protein ratios.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Cognition Disorders / cerebrospinal fluid*
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Parkinson Disease / complications*
  • Peptide Fragments / cerebrospinal fluid*
  • ROC Curve
  • Severity of Illness Index
  • alpha-Synuclein / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*


  • Amyloid beta-Peptides
  • Peptide Fragments
  • alpha-Synuclein
  • amyloid beta-protein (1-42)
  • tau Proteins