Circulating oligodendrocyte-derived extracellular vesicle surface markers in athletes exposed to repetitive head...

Repetitive head impacts (RHI) are increasingly recognized as potential contributors to long-term neurological consequences. Current clinical assessments rely primarily on symptoms and acute neurological findings, limiting the ability to detect and longitudinally monitor biological responses that may occur in the absence of clinically recognized concussion. This exploratory study investigated surface-associated biomarkers on circulating oligodendrocyte-derived extracellular vesicles (ODEs) as candidate blood markers of biological responses associated with RHI exposure.

Plasma ODEs were captured using an anti-myelin oligodendrocyte glycoprotein (MOG) antibody and probed for ciliary neurotrophic factor (CNTF), interleukin-1β (IL-1β), and α-synuclein (α-syn), selected to reflect neural repair, neuroinflammatory, and neurodegenerative processes, respectively. Unlike conventional EV analyses focused primarily on intravesicular cargo, this platform preserves vesicle integrity and quantifies biomolecules associated with the external surface of captured ODEs. Assays for each biomarker were analytically characterized prior to application to the athletic cohorts.

Longitudinal measurements were obtained from boxing and mixed martial arts fighters (n = 18; pre-event to 5 weeks post-event), high school American football players (n = 34; sampled monthly from July through November), and college rugby players (n = 14; sampled 3-4 times annually from 2014 to 2017). High school cross-country runners (n = 68) served as an athletic comparison group with substantially lower expected exposure to direct head impacts. Biomarker levels remained generally stable in the cross-country cohort, whereas subsets of combat and collision-sport athletes exhibited longitudinal changes in ODE-associated biomarkers, including individuals without clinically recognized concussion or neurological symptoms. Individual head-impact burden and relevant clinical confounders were not systematically quantified, precluding establishment of an exposure-response relationship.

Surface-associated biomarkers on circulating ODEs demonstrated measurable longitudinal changes in subsets of athletes with expected exposure to RHI. These exploratory findings support prospective studies combining ODE-associated biomarker measurements with quantitative head-impact monitoring, clinical characterization, neuroimaging, and neurological outcomes to determine their biological and clinical significance.