{Reference Type}: Journal Article {Title}: Molecular beacon-based detection of circulating microRNA-containing extracellular vesicle as an α-synucleinopathy biomarker. {Author}: Yu Z;Zheng Y;Cai H;Li S;Liu G;Kou W;Yang C;Cao S;Chen L;Liu X;Wan Z;Zhang N;Li X;Cui G;Chang Y;Huang Y;Lv H;Feng T; {Journal}: Sci Adv {Volume}: 10 {Issue}: 20 {Year}: 2024 May 17 {Factor}: 14.957 {DOI}: 10.1126/sciadv.adl6442 {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.