{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:37:43Z","timestamp":1791959863175,"version":"4.3.4"},"reference-count":43,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"\n Importance<\/jats:title>\n Exposure to repetitive head impacts (RHI) is associated with increased risk of a range of neurodegenerative diseases, including Alzheimer disease and amyotrophic lateral sclerosis. However, while the protein pathologies in the brains of individuals with the RHI-associated pathology of chronic traumatic encephalopathy (CTE) are well described, the spinal cord pathology in at-risk individuals remains poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate spinal cord pathologies associated with RHI exposure or CTE neuropathologic change (CTE-NC) in the brain.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This case-control study of a retrospective autopsy series (June 2019 to August 2025) was performed among autopsied individuals who served as RHI-exposed cases or controls in a multicenter brain bank collaboration. Data analysis was performed from January 2024 to November 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n RHI history and CTE-NC presence.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Informant-reported clinical history as well as symptoms and immunohistochemistry for phosphorylated tau (p-tau), phosphorylated TAR DNA-binding protein 43 (p-TDP-43), \u03b1-synuclein, and amyloid-\u03b2 (A\u03b2), as well as amyloid precursor protein and human leukocyte antigen DR.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Of 70 autopsied individuals (62 male, 8 female; mean [SD] age, 64.40 [13.94] years), 20 showed CTE-NC in the brain. All cases with CTE-NC exhibited spinal cord p-tau deposits, especially in cases aged 65 years or older with prior RHI (n\u2009=\u200914), often showing extensive spinal tau pathology as both neuronal (all 14 cases) and astrocytic (12 of 14 cases [86%]) p-tau deposits. Spinal p-tau pathology was associated with microglial activation and motor symptoms. Notably, among the individuals with CTE-NC and prior RHI who were aged 65 years or older, additional spinal protein pathologies were present, comprising p-TDP-43 inclusions (9 of 14 cases [64%]), A\u03b2 deposits (13 of 14 cases [93%]), and \u03b1-synuclein deposits (7 of 14 cases [50%]), with all 4 of these pathologies present in 4 individuals (29%). In total, across all 20 CTE-NC cases, p-TDP-43 inclusions were confined to the spinal cord in 5 of the 10 individuals with spinal p-TDP-43 pathology. In contrast, among 50 individuals without CTE-NC, typically sparse p-tau deposits were seen in only 27 (54%). Among the 23 confirmed cases with a history of RHI, 16 (70%) exhibited CTE-NC, while 7 (30%) did not. Spinal tau pathology was more severe in those with CTE-NC; however, astrocytic tau pathology was also present in the group without CTE-NC, unlike in controls without RHI or CTE.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This case-control study provides autopsy evidence of a high prevalence of complex spinal pathology in individuals with CTE-NC, supporting the concept of trauma-related encephalomyelopathy. The frequent co-occurrence of p-TDP-43, A\u03b2, and \u03b1-synuclein pathologies in individuals aged 65 years or older with CTE-NC suggests that cumulative trauma might contribute to widespread misfolded protein aggregation.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.5421","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T16:00:38Z","timestamp":1769443238000},"page":"231","source":"Crossref","is-referenced-by-count":5,"title":["Spinal Cord Tau and Protein Copathologies Associated With Chronic Traumatic Encephalopathy"],"prefix":"10.1001","volume":"83","author":[{"given":"Hidetomo","family":"Tanaka","sequence":"first","affiliation":[{"name":"Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Black","sequence":"additional","affiliation":[{"name":"School of Psychology and Neuroscience, University of 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