Serum alpha-synuclein in restless legs syndrome

Study Objectives: To determine any correlation between serum alpha-synuclein (α-syn) concentrations and restless legs syndrome (RLS), and to explore the impact of intravenous iron supplementation on serum α-syn levels. Methods: We collected clinical data on 113 RLS patients in whom serum α-syn levels were quantified using an ELISA kit and compared to a group of 45 age-matched controls. A subset of nine RLS patients who received intravenous (IV) iron underwent pre- and post-treatment blood sampling to assess α-syn and ferritin response. Results: A family history of RLS was reported by 62.8% of patients, and current dopaminergic augmentation was observed in 31.0%. Low serum ferritin levels below 75 μg/L were seen in 39.8%. Serum α-syn levels were found to be significantly decreased in RLS patients (mean: 7.7 ng/mL) compared to controls (mean: 10.7 ng/mL), p<.05. Stratification based on sex, age, and age of onset, did not reveal significant differences in α-syn levels. In nine RLS patients who received IV iron treatment, a linear correlation between fold change in α-syn and ferritin was observed (R: 0.7, p<.05). The temporal relation between serum α-syn and IV iron treatment showed a gradual decline of α-syn and ferritin by time correlation (p=.023, R: -.739). Conclusion: In our study of 113 RLS participants, serum α-syn levels were decreased in RLS patients compared to healthy controls, and increased in the nine patients who received IV iron treatment in correlation with ferritin. This correlation could suggest a mechanism for reduced dopamine transmission in RLS.