Department of Pathophysiology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Sci Adv. 2024 May 17;10(20):eadl6442. doi: 10.1126/sciadv.adl6442. Epub 2024 May 15.
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.
早期和准确诊断α-突触核蛋白病具有挑战性，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测定法来评估血浆中含有 microRNA 的细胞外囊泡 (EV)。我们从中国的八个中心招募了 1203 名参与者，包括健康对照组 (HCs) 和孤立性 REM 睡眠行为障碍 (iRBD)、α-突触核蛋白病或非 α-突触核蛋白病患者。与非 α-突触核蛋白病患者和 HCs 相比，α-突触核蛋白病患者（包括前驱期 iRBD）的血浆 miR-44438 含量的 EV 水平显著升高。然而，帕金森病 (PD) 和多系统萎缩之间没有显著差异。miR-44438 含量的 EV 水平与 PD 患者的年龄和 Hoehn 和 Yahr 分期呈负相关，表明与疾病进展有潜在关联。此外，经过 16.3 个月的纵向分析显示，PD 患者的 miR-44438 含量的 EV 水平显著下降。这些结果强调了血浆 miR-44438 含量的 EV 作为早期检测和监测 α-突触核蛋白病进展的生物标志物的潜力。
