BACKGROUND α-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 α-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 α-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 α-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.

中文翻译：

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快速眼动睡眠行为障碍中的 SNCA 低甲基化是帕金森病的潜在生物标志物。

背景 α-突触核蛋白与帕金森病 (PD) 的发病机制有关，但尚未在特发性快速眼动睡眠行为障碍 (iRBD) 中对其进行彻底研究。目的：我们旨在探讨 iRBD 患者在遗传和/或蛋白质水平上是否存在不同的 α-突触核蛋白分布。方法 我们在本研究中纳入了 30 名 iRBD 患者、30 名 PD 患者和 30 名年龄和性别匹配的健康对照 (HC)。使用亚硫酸氢盐测序和定量逆转录聚合酶链反应确定 SNCA 甲基化和 mRNA 水平。使用 Meso Scale Discovery 测量外泌体 α-突触核蛋白的血浆水平。结果 SNCA 甲基化在 HC、iRBD 和 PD 组之间显示出不同的分布（HC 对 RBD：p = 0.011；HC 对 PD：p < 0.001；RBD 对 PD：p = 0。027)。然而，与 HC 患者相比，PD 患者的血浆外泌体 α-突触核蛋白水平仅升高（p = 0.027），并且仅与 PD 组的 SNCA 甲基化相关（p = 0.030，r = -0.397）。结论 iRBD 患者和 PD 患者均存在白细胞中 SNCA 低甲基化，表明 SNCA 甲基化可能是早期 PD 诊断的潜在生物标志物。