CSF biomarkers and clinical progression of Parkinson disease

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 alpha-synuclein (alpha Syn), beta-amyloid 1-42 (A beta(42)), 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 aSyn within the PD group were associated with progression of motor symptoms and cognitive decline over 2 years, indicated by significant relationships between aSyn and change in Hoehn and Yahr (beta = 0.394, p = 0.043), Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III) (beta = 0.449, p = 0.013), Timed Up and Go (beta = 0.406, p = 0.023), and A Quick Test of Cognitive Speed (beta = 0.423, p = 0.018). Lower levels of A beta(42) 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, beta = 0.350, p = 0.045; Hoehn and Yahr, beta = 0.366, p = 0.038). Conclusion: We found evidence of a link between higher levels of aSyn at baseline and worsening of motor symptoms and cognitive speed over 2 years in PD. Increased alpha Syn might be a marker of more intense synaptic degeneration in PD. The results indicate that cortical amyloid pathology (low CSF A beta(42)) is associated with memory decline.