The repetitive head impacts (RHIs) to which contact sport participants are exposed are a risk factor for chronic traumatic encephalopathy (CTE), which can affect relatively young individuals. Butler et al. now characterize the early cellular changes that might lead to CTE in young athletes exposed to RHIs.

To examine brain cell responses to RHIs, the authors performed single-nucleus RNA sequencing on post-mortem cortical tissue from young (<51 years of age) RHI-exposed individuals, with or without CTE pathology, and control individuals. The number of years of RHI exposure correlated with the number of microglial subtypes with inflammatory gene expression profiles and endothelial cells expressing inflammation-related genes. RHI exposure was also associated with altered neuronal synapse-related gene expression and neuron loss.