Cerebrospinal Fluid Phosphorylated Alpha‐Synuclein in Newly Diagnosed Parkinson's Disease

BACKGROUND: Alpha-synuclein (α-syn), phosphorylated at serine 129 (pS129-α-syn), is a potential biomarker for Parkinson's disease (PD) because it is the predominant α-syn species found in Lewy bodies. METHODS: We developed an in-house SIMOA assay, using commercially available components, to quantify pS129-α-syn in CSF. The clinical utility of the assay was tested in CSF from 120 patients with PD from the Norwegian ParkWest longitudinal study and 29 normal controls. Prior measurements of CSF total (t)-α-syn and the pS129-α-syn/t-α-syn ratio were included for comparison. RESULTS: The lower limit of quantification of the in-house assay used to analyze CSF samples from participants was 0.57 pg/mL, which was well below the observed concentrations of endogenous pS129-α-syn in CSF. Median CSF pS129-α-syn levels were slightly lower in PD patients compared to controls (5.7 pg/mL vs. 6.5 pg/mL), but the difference was not significant in the unadjusted (p = 0.404) or adjusted analyses (p = 0.270). There was no difference in the pS129-α-syn/t-α-syn ratio between patients and controls. Using linear mixed-effects models, we found no association between baseline pS129-α-syn or the pS129-α-syn/t-α-syn ratio and motor or cognitive decline over a 10-year period. CONCLUSION: We developed and applied an in-house SIMOA that reliably quantifies pS129-α-syn in CSF samples. This study does not indicate a role for CSF pS129-α-syn or the pS129-α-syn/t-α-syn ratio as clinically useful diagnostic or prognostic biomarkers in PD.