Total CSF α-synuclein is lower in de novo Parkinson patients than in healthy subjects

Several studies demonstrated reduced CSF α-synuclein values in patients with advanced Parkinson's disease (PD). Values in drug-naïve PD subjects and healthy controls (HC) have not yet been reported. We measured CSF values including α-synuclein in a cohort of 78 previously untreated PD patients and 48 HC subjects. Measurements of total α-synuclein concentrations were performed using two independently operated immunoassays, i.e., one academia-based and previously validated (ELISA 1), the other industry-based, renewable and commercially available (ELISA 2). Mean values for CSF α-synuclein were significantly lower in de novo PD patients when compared to HC subjects, as demonstrated by both assays (ELISA 1, p=0.049; ELISA 2, p=0.005; combined, p=0.002). Using the renewable ELISA 2, CSF α-synuclein concentrations of 1884.31 pg/ml or less showed a sensitivity of 0.91 and a specificity of 0.25 for the diagnosis of Parkinson's disease. The corresponding area-under-the-curve value was 0.65 (confidence interval, 0.554-0.750), which was statistically significant (p=0.004). Total CSF α-synuclein is reduced early in the course of Parkinson's disease, as measured by two independent ELISA platforms at the time of enrolment, and this reduction appears independent from drug treatment. Follow-up investigations will determine the usefulness of CSF α-synuclein values as markers of progression in individual subjects.