Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurology, Ruijin Hospital North affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Parkinsons Dis. 2020;10(3):1023-1031. doi: 10.3233/JPD-201912.
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).
We aimed to explore whether there were different distributions of α-synuclein at a genetic and/or protein level in patients with iRBD.
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.
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).
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.
α-突触核蛋白与帕金森病（PD）的发病机制有关，但在特发性快速眼动睡眠行为障碍（iRBD）中尚未得到彻底研究。
我们旨在探讨 iRBD 患者是否存在α-突触核蛋白在遗传和/或蛋白水平上的不同分布。
我们纳入了 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者（HCs）。采用亚硫酸氢盐测序和定量逆转录聚合酶链反应检测 SNCA 甲基化和 mRNA 水平。采用 Meso Scale Discovery 测量血浆外泌体α-突触核蛋白水平。
SNCA 甲基化在 HC、iRBD 和 PD 组之间存在不同的分布（HC 与 RBD 组：p=0.011；HC 与 PD 组：p<0.001；RBD 与 PD 组：p=0.027）。然而，与 HCs 相比，仅 PD 患者的血浆外泌体α-突触核蛋白水平升高（p=0.027），且仅在 PD 组与 SNCA 甲基化相关（p=0.030，r=-0.397）。
白细胞中 SNCA 低甲基化既存在于 iRBD 患者，也存在于 PD 患者中，表明 SNCA 甲基化可能是早期 PD 诊断的潜在生物标志物。
