Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy
- Guanlan Dong
- Chanthia C. Ma
- 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 Spurlock
- Ann C. McKee
- August Yue Huang
- Michael B. Miller
- Eunjung Alice Lee
- Christopher A. Walsh
2025-10-30
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.