Non‐Targeted Analysis of Extracellular Vesicle‐Enriched Plasma Proteome Between Early and Late Rugby Playing Career

Repetitive high-impact collisions experienced by rugby players may predispose them to neurodegenerative conditions, yet the biological processes underpinning this risk remain poorly understood. This study investigates whether the proteome of plasma extracellular vesicles (EV) could serve as early, minimally invasive biomarkers of neurodegenerative risk in athletes exposed to repeated head impacts. By comparing the EV proteome of professional rugby players, younger academy athletes, and non-collision sport controls, we identified specific proteins with known neuroprotective roles that were depleted in long-serving rugby professionals. These alterations suggest systemic biological changes related to prolonged exposure to collisions. Our findings provide novel insight by highlighting the potential of EV-based proteomic profiling as a tool for early detection and monitoring of neurodegeneration-related processes in at-risk athletic populations. This approach could ultimately inform strategies for risk stratification, early intervention, and tailored clinical monitoring in collision sport athletes.