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

Article type: Research Article

Authors: Zhao, Aonan^{a; 1} | Li, Yuanyuan^{a; 1} | Niu, Mengyue^a | Li, Guanglu^a | Luo, Ningdi^a | Zhou, Liche^a | Kang, Wenyan^b | Liu, Jun^{a; c; *}

Affiliations: [a] Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated with the Shanghai Jiao Tong University School of Medicine, Shanghai, China | [b] Department of Neurology, Ruijin Hospital North affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China | [c] CAS Center for Excellence in Brain Science and Intelligence Technology, Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China

Correspondence: [*] Correspondence to: Prof. Jun Liu, MD, PhD, Department of Neurology and Institute of Neurology, Ruijin Hospital affiliated with the Shanghai Jiao Tong University School of Medicine, No.197, Ruijin Second Road, Shanghai 200025, China. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: 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.

Keywords: Parkinson’s disease, SNCA hypomethylation, exosome, biomarker

DOI: 10.3233/JPD-201912

Journal: Journal of Parkinson's Disease, vol. 10, no. 3, pp. 1023-1031, 2020