Concussion-based ApoE4 and Lipid Prodromal Biomarkers: The UK Rugby Health Study

Neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) have been associated with long-term effects of concussions, particularly in contact sport athletes. Lipid dysregulation has emerged as a potential contributor to neuronal damage and could serve as an early biomarker of brain pathology. This study aimed to investigate serum lipid biomarkers in retired rugby players with a history of concussion to explore their diagnostic relevance and potential link to neurodegenerative disease risk. A comparative analysis was conducted comparing serum levels of ApoE4, 24-hydroxycholesterol (24-HC), 25-HC, 27-HC, total triglycerides, and ceramide between concussed retired rugby players and non-contact healthy controls. ELISA-based quantification and statistical comparisons were used to identify significant group differences. Retired rugby players exhibited significantly lower serum 24-HC and significantly higher levels of ApoE4, 27-HC, triglycerides, and ceramide compared to controls. No significant difference was found in 25-HC, though some concussed individuals showed elevated levels. These findings align with previous reports in AD, PD, and ALS populations, supporting lipid dysregulation as a hallmark of neurodegenerative progression. Alterations in lipid profiles among concussed athletes suggest potential roles for ApoE4, 24-HC, 27-HC, ceramide, and triglycerides as early biomarkers for concussion-induced neurodegeneration. These findings may guide future diagnostics and post-care strategies for at-risk populations.