Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy

chronic traumatic encephalopathy (cte) is a neurodegenerative disease linked to exposure to repetitive head impacts (rHI), yet little is known about its pathogenesis. Applying two single-cell whole-genome sequencing methods to hundreds of neurons from prefrontal cortex of 15 individuals with cte and 4 with rHI without cte, we revealed increased somatic single-nucleotide variants in cte, exhibiting a pattern previously reported in Alzheimer’s disease (AD). Furthermore, we discovered high burdens of somatic small insertions and deletions in a subset of cte individuals, resembling a known pattern, ID4, also found in AD. Our results suggest that neurons in cte experience stereotyped mutational processes shared with AD; the absence of similar changes in rHI neurons without cte suggests that cte involves mechanisms beyond rHI alone.