Guanlan Dong, C. Chanthia, Shulin Mao, Katherine Sun-Mi Brown, Samuel M. Naik, Gannon A. McDonough, Samadhi P. Wijethunga, Junho Kim, Samantha L. Kirkham, Diane D. Shao, Jonathan D. Cherry, Madeline Uretsky, Elizabeth E. Spurlock, Ann C. McKee, August Yue Huang, Michael B. Miller, Eunjung Alice Lee, Christopher A. Walsh
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.