Molecular beacon–based detection of circulating microRNA-containing extracellular vesicle as an α-synucleinopathy biomarker
Zhenwei Yu, Yuanchu Zheng, Huihui Cai, Siming Li, Genliang Liu, Wenyi Kou, Chen Yang, Shuang‐Shuang Cao, Lei Chen, Xuedong Liu, Zhirong Wan, N. Zhang, Xiaohong Li, Guiyun Cui, Ying Chang, Yue Huang, Hong Lv, Tao Feng
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.