Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy
Dong, G.; Ma, C. C.; Mao, S.; Naik, S. M.; Brown, K. S.-M.; McDonough, G. A.; Kim, J.; Kirkham, S. L.; Cherry, J.; Uretsky, M.; Spurlock, E.; McKee, A.; Huang, A. Y.; Miller, M. B.; Lee, E. A.; Walsh, C. A.
Show abstract
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is 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, revealed increased somatic single-nucleotide variants in CTE, resembling a pattern previously reported in Alzheimers disease (AD). Furthermore, we discovered remarkably 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.
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