There have been no longitudinal studies on a-synuclein as a potential biomarker for the progression of Parkinson's disease (PD). Here, blood plasma 'total a-synuclein' and 'Ser-129 phosphorylated α-synuclein' were assayed at 4-6 monthly intervals from a cohort of 189 newly-diagnosed patients with PD. For log-transformed data, plasma total a-synuclein levels increased with time for up to 20 yrs after the appearance of initial symptoms (p 5 0.012), whereas phosphorylated α-synuclein remained constant over this same period. The mean level of phosphorylated a-synuclein, but not of total a-synuclein, was higher in the PD plasma samples taken at first visit than in single samples taken from a group of 91 healthy controls (p50.012). Overall, we conclude that the plasma level of phosphorylated α-synuclein has potential value as a diagnostic tool, whereas the level of total a-synuclein could act as a surrogate marker for the progression of PD.
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