Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls

Objective: To analyze longitudinal levels of CSF biomarkers in drug-naive patients with Parkinson disease (PD) and healthy controls (HC), examine the extent to which these biomarker changes relate to clinical measures of PD, and identify what may influence them. Methods: CSF alpha-synuclein (alpha-syn), total and phosphorylated tau (t- and p-tau), and beta-amyloid 1-42 (A beta 42) were measured at baseline and 6 and 12 months in 173 patients with PD and 112 matched HC in the international multicenter Parkinson's Progression Marker Initiative. Baseline clinical and demographic variables, PD medications, neuroimaging, and genetic variables were evaluated as potential predictors of CSF biomarker changes. Results: CSF biomarkers were stable over 6 and 12 months, and there was a small but significant increase in CSF A beta 42 in both patients with patients with PD and HC from baseline to 12 months. The t-tau remained stable. The p-tau increased marginally more in patients with PD than in HC. alpha-syn remained relatively stable in patients with PD and HC. Ratios of p-tau/t-tau increased, while t-tau/A beta 42 decreased over 12 months in patients with PD. CSF biomarker changes did not correlate with changes in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale motor scores or dopamine imaging. CSF alpha-syn levels at 12 months were lower in patients with PD treated with dopamine replacement therapy, especially dopamine agonists. Conclusions: These core CSF biomarkers remained stable over 6 and 12 months in patients with early PD and HC. PD medication use may influence CSF alpha-syn. Novel biomarkers are needed to better profile progressive neurodegeneration in PD.