CSF biomarkers and clinical progression of Parkinson disease

Neurology. 2015 Jan 6;84(1):57-63. doi: 10.1212/WNL.0000000000001098. Epub 2014 Nov 19.


Objective: To investigate whether certain CSF biomarkers at baseline can predict future progression of motor symptoms and cognitive decline in patients with Parkinson disease (PD).

Methods: Patients and controls were recruited from hospitals in southern Sweden as part of the prospective and longitudinal Swedish BioFinder Study. In the present study, we included 42 patients with PD and 69 controls who had clinical assessment and lumbar puncture at baseline. Baseline CSF samples were analyzed for α-synuclein (αSyn), β-amyloid 1-42 (Aβ42), tau, phosphorylated tau, and neurofilament light. Associations between CSF markers at baseline and change in clinical characteristics after 2 years of follow-up were investigated using multivariate models adjusting for age, sex, disease duration, and levodopa-equivalent daily dose.

Results: Higher levels of αSyn within the PD group were associated with progression of motor symptoms and cognitive decline over 2 years, indicated by significant relationships between αSyn and change in Hoehn and Yahr (β = 0.394, p = 0.043), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (β = 0.449, p = 0.013), Timed Up and Go (β = 0.406, p = 0.023), and A Quick Test of Cognitive Speed (β = 0.423, p = 0.018). Lower levels of Aβ42 were associated with worsening of performance on delayed memory recall (F = 5.834, p = 0.022). Finally, high levels of phosphorylated tau were associated with worsening in motor symptoms (UPDRS-III, β = 0.350, p = 0.045; Hoehn and Yahr, β = 0.366, p = 0.038).

Conclusion: We found evidence of a link between higher levels of αSyn at baseline and worsening of motor symptoms and cognitive speed over 2 years in PD. Increased αSyn might be a marker of more intense synaptic degeneration in PD. The results indicate that cortical amyloid pathology (low CSF Aβ42) is associated with memory decline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Case-Control Studies
  • Cognition Disorders / cerebrospinal fluid*
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Movement Disorders / cerebrospinal fluid*
  • Movement Disorders / etiology
  • Movement Disorders / physiopathology
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neuropsychological Tests
  • Parkinson Disease / cerebrospinal fluid*
  • Parkinson Disease / complications
  • Parkinson Disease / physiopathology
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Prognosis
  • Prospective Studies
  • Sweden
  • alpha-Synuclein / cerebrospinal fluid*
  • tau Proteins / cerebrospinal fluid*
  • tau Proteins / metabolism


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