Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson disease

Objective: Biomarkers are required for the diagnosis and monitoring of disease progression in Parkinson disease (PD). To date, most studies have concentrated on alpha-Synuclein (alpha-Syn), a protein involved in Parkinson disease pathogenesis, as a potential biomarker, with inconsistent outcomes. Recently, naturally occurring autoantibodies against alpha-Syn (alpha-Syn-nAbs) have been detected in the serum of patients with PD. They represent a putative diagnostic marker for PD. Methods: We established and validated an ELISA to quantify alpha-Syn-nAbs in serum samples. We analyzed serum samples from 62 patients with PD, 46 healthy controls (HC), and 42 patients with Alzheimer disease (AD) using this newly established ELISA. Additionally, serum levels of endogenous alpha-Syn were measured. Results: There was a significant difference in alpha-Syn-nAbs levels between the investigated groups (p = 0.005; Kruskal-Wallis test). Levels of alpha-Syn-nAbs were significantly lower in patients with PD compared to HC (p < 0.05; Dunn multiple comparison post hoc test) or patients with AD (p, 0.05). Furthermore, we detected no difference between patients with AD and HC. The sensitivity and specificity of the assay for patients with PD vs HC were 85% and 25%, respectively. The alpha-Syn-nAbs levels did not correlate with age, Hoehn & Yahr status, or duration of disease. Endogenous alpha-Syn had no influence on alpha-Syn-nAbs levels in sera. Conclusions: Using a well-validated assay, we detected reduced alpha-Syn-nAbs levels in patients with PD compared to patients with AD and HC. The assay did not achieve criteria for use as a diagnostic tool to reliably distinguish PD from HC. Further studies are needed to assess alpha-Syn-nAbs as a biomarker in PD. Neurology (R) 2013;80:169-175