Neuron inflammation and loss is correlated with years of repetitive head impacts, increasing susceptibility to CTE in former contact sports athletes under age 51
By Emily Sugg. This article was initially published in the 12/11/25 Edition of our Concussion Update newsletter; please consider subscribing.
A recent study published in Nature found that multiple years of repetitive head impacts (RHIs) can cause changes in the brain at the cellular level that precede and may underlie clustering of hyperphosphorylated tau protein (p-tau), a key marker of chronic traumatic encephalopathy (CTE). CTE is a progressive brain disorder resulting from repeated head trauma, including RHIs. This study, based on donated brain tissue, found that these brain changes correlated with the number of years that study participants had played contact sports.
Authors Morgane Butler et al. surmise that these changes may also help explain early symptoms and development of the disease that are not fully explained by p-tau clustering. Gaining insight into how these changes in the brain unfold, especially how to identify them earlier in life, will enable professionals to study disease progression more effectively. This knowledge will also allow clinicians to better understand structural brain changes in contact sport athletes, investigate prevention strategies, and improve timely intervention.
Dr. Morgane Butler and her colleagues from Boston University Chobanian & Avedisian School of Medicine used single-nucleus RNA sequencing on donated brain tissue to observe differences in gene expression between individuals with different amounts of exposure to RHIs: a control group with no history of contact sports, 8 American football and soccer players with no history of a CTE diagnosis but who had been exposed to RHI throughout their sporting career, and 11 contact sport athletes with low-stage CTE (Stage 1 or 2 CTE, which have much milder pathology than stages 3 or 4). They found that people exposed to RHI had an average of 56% fewer excitatory neurons in the brain sulci – the folds of the brain that take the most force during a head impact. In addition, the researchers identified markers of inflammation related to microglia and endothelial cells, astrocyte cell death, and altered gene expression. Some individuals in their RHI sample had no signs of tau protein clustering, suggesting that neural damage may start much earlier than CTE. As CTE advances, increasing tau clustering makes the loss of brain cells even more severe.
This study is the first to analyze brain changes from exposure to repeated head trauma in a younger (under age 51) population. A limitation is that the study only samples a small area of brain tissue. CTE is typically a “patchy disease,” meaning that sampling could have missed important cellular responses in other regions. With that being said, these findings support that RHI causes brain damage in people under age 51 that is identifiable before the development of p-tau clusters that are characteristic of CTE.