Association between probable REM sleep behavior disorder and increased dermal alpha-synuclein deposition in Parkinson's disease

Abstract

Introduction: Many patients with Parkinson's disease suffer from REM sleep behavior disorder, potentially preceding the onset of motor symptoms. Phospho-alpha-synuclein is detectable in skin biopsies of patients with isolated REM sleep behavior disorder several years prior to the onset of manifest PD, but information on the association between dermal phospho-alpha-synuclein deposition and REM sleep behavior disorder in patients with manifest PD is limited. We therefore aimed to investigate the alpha-synuclein burden in dermal peripheral nerve fibers in patients with Parkinson's disease with and without REM sleep behavior disorder.

Methods: Patients with Parkinson's disease (n = 43) who had undergone skin biopsy for the immunohistochemical detection of phosphorylated alpha-synuclein were screened for REM sleep behavior disorder using RBDSQ and Mayo Sleep Questionnaire. Skin biopsies from 43 patients with isolated polysomnography-confirmed REM sleep behavior disorder were used as comparators.

Results: Dermal alpha-synuclein deposition was more frequently found (81.8% vs. 52.4%, p = 0.05) and was more abundant (p = 0.01) in patients with Parkinson's disease suffering from probable REM sleep behavior disorder compared to patients without REM sleep behavior disorder and was similar to patients with isolated REM sleep behavior disorder (79.1%).

Conclusion: The phenotype of REM sleep behavior disorder is associated with high amounts of dermal alpha-synuclein deposition, demonstrating a strong involvement of peripheral nerves in patients with this non-motor symptom and may argue in favor of REM sleep behavior disorder as an indicator of a "body-predominant" subtype of Parkinson's disease.