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Abstract：
Early and precise diagnosis of α-synucleinopathies is challenging but critical. In this study, we developed a molecular beacon-based assay to evaluate microRNA-containing extracellular vesicles (EVs) in plasma. We recruited 1203 participants including healthy controls (HCs) and patients with isolated REM sleep behavior disorder (iRBD), α-synucleinopathies, or non-α-synucleinopathies from eight centers across China. Plasma miR-44438-containing EV levels were significantly increased in α-synucleinopathies, including those in the prodromal stage (e.g., iRBD), compared to both non-α-synucleinopathy patients and HCs. However, there are no significant differences between Parkinson\'s disease (PD) and multiple system atrophy. The miR-44438-containing EV levels negatively correlated with age and the Hoehn and Yahr stage of PD patients, suggesting a potential association with disease progression. Furthermore, a longitudinal analysis over 16.3 months demonstrated a significant decline in miR-44438-containing EV levels in patients with PD. These results highlight the potential of plasma miR-44438-containing EV as a biomarker for early detection and progress monitoring of α-synucleinopathies.
摘要：
α-突触核蛋白病的早期和精确诊断具有挑战性，但至关重要。在这项研究中,我们开发了一种基于分子信标的检测方法来评估血浆中含有microRNA的细胞外囊泡(EV).我们招募了1203名参与者，包括健康对照（HCs）和孤立性REM睡眠行为障碍（iRBD）患者，α-突触核蛋白病,来自中国八个中心的非α-突触核蛋白病。在α-突触核蛋白病中，血浆含miR-44438的EV水平显着增加，包括处于前驱阶段的那些(例如，iRBD)，与非α-突触核蛋白病患者和HC相比。然而,帕金森病(PD)与多系统萎缩无显著差异。含miR-44438的EV水平与PD患者的年龄和Hoehn和Yahr分期呈负相关，提示与疾病进展的潜在关联。此外，一项超过16.3个月的纵向分析显示,PD患者中含有miR-44438的EV水平显著下降.这些结果突出了含miR-44438的血浆EV作为α-突触核蛋白病早期检测和进展监测的生物标志物的潜力。
