SNCA Hypomethylation in Rapid Eye Movement Sleep Behavior Disorder Is a Potential Biomarker for Parkinson's Disease

Background: alpha-Synuclein has been related to the pathogenesis of Parkinson's disease (PD), but it has not thoroughly been investigated in idiopathic rapid eye movement sleep behavior disorder (iRBD). Objective: We aimed to explore whether there were different distributions of alpha-synuclein at a genetic and/or protein level in patients with iRBD. Methods: We included 30 patients with iRBD, 30 patients with PD, and 30 age- and sex-matched healthy controls (HCs) in this study. The SNCA methylation and mRNA levels were determined using bisulfite sequencing and quantitative reverse transcription polymerase chain reaction. The plasma levels of exosome alpha-synuclein were measured using Meso Scale Discovery. Results: SNCA methylation showed different distribution among HC, iRBD and PD groups (HC vs RBD: p = 0.011; HC vs PD: p < 0.001; RBD vs PD: p = 0.027). However, plasma exosomal alpha-synuclein levels were only elevated in patients with PD compared to those in HCs (p = 0.027), and were associated with the SNCA methylation only in the PD group (p = 0.030, r = -0.397). Conclusion: SNCA hypomethylation in leukocytes existed both in patients with iRBD and those with PD, indicating that SNCA methylation could be a potential biomarker for early PD diagnosis.