Abstract
Background and PurposeRapid eye movement (REM) Rapid eye movement sleep behavior disorder (RBD) is a common non-motor symptom of PD. However, the association between the SNCA rs3910105 genotype and RBD in Parkinson’s disease (PD) remains unclear.MethodsThis study used Parkinson’s Progression Markers Initiative (PPMI) data and included 270 patients with newly diagnosed PD without RBD who were divided into SNCA rs3910105 C carriers (CC+CT; n = 187) and TT carriers (n = 83). They were followed up for 5 years to identify the development of RBD. To investigate the influence of cerebrospinal fluid (CSF) alpha-synuclein (α-syn) and β-amyloid 1–42 (Aβ42) in the association between rs3910105 and RBD, the patients were additionally classified into “high-level” and “low-level” groups using cutoff values for CSF α-syn and Aβ42 levels.ResultsAt baseline, the rs3910105 C allele group had lower CSF α-syn and Aβ42 levels than the TT group. During the 5.0-year follow-up, the rs3910105 C allele group had a higher incidence of RBD than the TT group. In the subgroup analyses, the effect of the rs3910105 C allele was not found in the “low-level” group. However, in the “high-level” group, the rs3910105 C allele independently increased the risk of RBD.ConclusionThe SNCA rs3910105 C allele might be a novel genetic risk factor for RBD development in PD, α-syn pathways might have a role in this association and more basic research would be needed to elucidate the mechanism in the future.
Highlights
Parkinson’s disease (PD) is an age-related neurodegenerative disease with a wide range of motor and non-motor symptoms (Chaudhuri et al, 2006; Bloem et al, 2021)
This study investigated the relationship of the SNCA rs3910105 C allele with the development of Rapid eye movement sleep behavior disorder (RBD) in patients with early PD using the Parkinson’s Progression Markers Initiative (PPMI) cohort
Our results showed that the SNCA rs3910105 C allele was associated with faster development of RBD in PD patients, suggesting that the SNCA rs3910105 C allele was a novel genetic risk factor for RBD
Summary
Parkinson’s disease (PD) is an age-related neurodegenerative disease with a wide range of motor and non-motor symptoms (Chaudhuri et al, 2006; Bloem et al, 2021). Rapid eye movement (REM) Rapid eye movement sleep behavior disorder (RBD) is a common non-motor symptom of PD that is characterized by the loss of normal muscle atonia during REM sleep and involves dreamenacting behavior (Dauvilliers et al, 2018; Miglis et al, 2021). RBD in patients with PD (Lee et al, 2010; Romenets et al, 2012). Given that CSF α-syn and Aβ42 levels inversely correlate with α-syn and Aβ pathology in the brain (Fagan et al, 2006; Wennström et al, 2013; Gold et al, 2021), this observation may support the notion that cerebral synucleinopathy or amyloidopathy contributes to the development of RBD. Rapid eye movement (REM) Rapid eye movement sleep behavior disorder (RBD) is a common non-motor symptom of PD. The association between the SNCA rs3910105 genotype and RBD in Parkinson’s disease (PD) remains unclear
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