{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:54:44Z","timestamp":1793260484976,"version":"4.5.0"},"reference-count":47,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"\n Importance<\/jats:title>\n \n Repetitive head impact (RHI) exposure is the chief risk factor for chronic traumatic encephalopathy (CTE). However, the occurrence and severity of CTE varies widely among those with similar RHI exposure. Limited evidence suggests that the\n APOE<\/jats:italic>\n \u03b54 allele may confer risk for CTE, but previous studies were small with limited scope.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To test the association between\n APOE<\/jats:italic>\n genotype and CTE neuropathology and related endophenotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cross-sectional genetic association study analyzed brain donors from February 2008 to August 2019 from the Veterans Affairs\u2013Boston University\u2013Concussion Legacy Foundation Brain Bank. All donors had exposure to RHI from contact sports or military service. All eligible donors were included. Analysis took place between June 2020 and April 2022.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n \n One or more\n APOE<\/jats:italic>\n \u03b54 or\n APOE<\/jats:italic>\n \u03b52 alleles.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n CTE neuropathological status, CTE stage (0-IV), semiquantitative phosphorylated tau (p-tau) burden in 11 brain regions (0-3), quantitative p-tau burden in the dorsolateral frontal lobe (log-transformed AT8+ pixel count per mm\n 2<\/jats:sup>\n ), and dementia.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 364 consecutive brain donors (100% male; 53 [14.6%] self-identified as Black and 311 [85.4%] as White; median [IQR] age, 65 [47-77] years) 20 years or older, there were 294 individuals with CTE and 70 controls. Among donors older than 65 years,\n APOE<\/jats:italic>\n \u03b54 status was significantly associated with CTE stage (odds ratio [OR], 2.34 [95% CI, 1.30-4.20]; false discovery rate [FDR]\u2013corrected\n P<\/jats:italic>\n \u2009=\u2009.01) and quantitative p-tau burden in the dorsolateral frontal lobe (\u03b2,\u20091.39 [95% CI, 0.83-1.94]; FDR-corrected\n P<\/jats:italic>\n \u2009=\u20092.37\u2009\u00d7\u200910\n \u22125<\/jats:sup>\n ). There was a nonsignificant association between\n APOE<\/jats:italic>\n \u03b54 status and dementia (OR,\u20092.64 [95% CI, 1.06-6.61]; FDR-corrected\n P<\/jats:italic>\n \u2009=\u2009.08). Across 11 brain regions, significant associations were observed for semiquantitative p-tau burden in the frontal and parietal cortices, amygdala, and entorhinal cortex (OR range, 2.45-3.26). Among football players, the\n APOE<\/jats:italic>\n \u03b54 association size for CTE stage was similar to playing more than 7 years of football. Associations were significantly larger in the older half of the sample. There was no significant association for CTE status. Association sizes were similar when donors with an Alzheimer disease neuropathological diagnosis were excluded and were reduced but remained significant after adjusting for neuritic and diffuse amyloid plaques. No associations were observed for\n APOE<\/jats:italic>\n \u03b52 status. Models were adjusted for age at death and race.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n APOE<\/jats:italic>\n \u03b54 may confer increased risk for CTE-related neuropathological and clinical outcomes among older individuals with RHI exposure. Further work is required to validate these findings in an independent sample.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2022.1634","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T11:34:02Z","timestamp":1656329642000},"page":"787","source":"Crossref","is-referenced-by-count":71,"title":["Association of\n APOE<\/i>\n Genotypes and Chronic Traumatic Encephalopathy"],"prefix":"10.1001","volume":"79","author":[{"given":"Kathryn","family":"Atherton","sequence":"first","affiliation":[{"name":"Boston University Bioinformatics Graduate Program, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Han","sequence":"additional","affiliation":[{"name":"Boston University Bioinformatics Graduate Program, Boston, Massachusetts"},{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyoon","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Cherry","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"},{"name":"VA Boston Healthcare System, Boston, Massachusetts"},{"name":"Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts"},{"name":"Department of Veterans Affairs Medical Center, Bedford, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Baucom","sequence":"additional","affiliation":[{"name":"Boston University Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Saltiel","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"},{"name":"VA Boston Healthcare System, Boston, Massachusetts"},{"name":"Department of Veterans Affairs Medical Center, Bedford, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Nair","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobak","family":"Abdolmohammadi","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Uretsky","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Muzamil","family":"Khan","sequence":"additional","affiliation":[{"name":"Boston University Bioinformatics Graduate Program, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Shea","sequence":"additional","affiliation":[{"name":"Boston University Bioinformatics Graduate Program, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Durape","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"},{"name":"Biostatistics & Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph N.","family":"Palmisano","sequence":"additional","affiliation":[{"name":"Boston University Alzheimer\u2019s Disease and CTE Centers, Boston University School of Medicine, Boston, Massachusetts"},{"name":"Biostatistics & Epidemiology Data Analytics Center, Boston University School of Public Health, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Fishberg Department of Neuroscience, Friedman Brain Institute, Ronald M. 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