Serum Alpha-synuclein in Restless Legs Syndrome

Aboud Tahanis; Vera Hashem; William Ondo

doi:10.1093/sleep/zsae217

Serum Alpha-synuclein in Restless Legs Syndrome

Sleep. 2024 Sep 16:zsae217. doi: 10.1093/sleep/zsae217. Online ahead of print.

Authors

Aboud Tahanis¹, Vera Hashem², William Ondo^{2

3}

Affiliations

¹ Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, Texas, USA.
² Department of Neurology, Methodist Neurological Institute, Houston, Texas, USA.
³ Department of Neurology, Weill Cornell Medical School, New York, New York, USA.

PMID: 39283300
DOI: 10.1093/sleep/zsae217

Abstract

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 9 RLS patients who received intravenous (IV) iron underwent pre- and post-treatment blood sampling to assess α-syn and ferritin response.

Results: 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<0.05. Stratification based on sex, age and age of onset, did not reveal significant differences in α-syn levels. In 9 RLS patients who received IV iron treatment, a linear correlation between fold change in α-syn and ferritin was observed (R: 0.7, p <0.05). The temporal relation between serum α-syn and IV iron treatment showed a gradual decline of α-syn and ferritin by time correlation (p = 0.023, R: -0.739).

Conclusion: In our study of 113 RLS subjects, serum α-syn levels were decreased in RLS patients compared to healthy controls and increased in the 9 patients who received IV iron treatment in correlation with ferritin. This correlation could suggest a mechanism for reduced dopamine transmission in RLS.

Keywords: SNCA; alpha-synuclein; dopamine; ferritin; iron; restless legs syndrome.

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