Proteomic Exploration of L1CAM+-Extracellular Vesicles from Plasma of Manifest and Prodromal Parkinson’s Disease

L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles (EVs) are being explored as a potential source of biomarkers for Parkinson's disease (PD) in peripheral blood. However, their utility remains controversial. In this study, we sought to investigate the proteome composition of L1CAM⁺-EVs isolated from human blood plasma and evaluate their potential as biomarkers for PD. L1CAM⁺-EVs were extracted from blood plasma using direct immunoprecipitation by employing magnetic beads coupled to an anti-L1CAM antibody. The Proximity Extension Assay platform, Olink Explore 3072, was used to analyze samples from 60 individuals: 20 healthy controls (HC), 20 patients with isolated REM sleep behavior disorder (iRBD), and 20 PD patients. Targeted proteomic analysis identified 2841 proteins in L1CAM⁺-EVs, of which 203 exhibited differential expression across groups. Although these changes were not statistically significant, after correction for multiple testing, a combination of 12 proteins could discriminate between PD and HC. Moreover, several proteins displayed trends toward upregulation or downregulation in PD and iRBD when compared with HC. These preliminary findings suggest that L1CAM⁺-EVs proteins show some potential as biomarkers for PD; however, further investigation and validation studies are required.