title: Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank.
abstract: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.|Mayo Graduate School, Mayo Clinic, 200 First St., Rochester, MN, 55905, USA.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: Bieniek
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.affiliation: VA Boston HealthCare System, 150 South Huntington Ave, Boston, MA, 02130, USA.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Cormier
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Walton
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Soto-Ortolaza
authors.affiliation: Department of Neurology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Amelia E
authors.initials: AE
authors.lastname: Johnston
authors.affiliation: Department of Neurology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: DeSaro
authors.affiliation: Department of Neurology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Boylan
authors.affiliation: Department of Neurology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.affiliation: Department of Neurology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA.
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.affiliation: Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.affiliation: VA Boston HealthCare System, 150 South Huntington Ave, Boston, MA, 02130, USA.|Department of Neurology and Pathology, Boston University Alzheimer's Disease Center and CTE Program, Boston University School of Medicine, Boston, MA, 02118, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.affiliation: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, FL, 32224, USA. dickson.dennis@mayo.edu.
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D001265:Athletic Injuries / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D020208:Brain Injury, Chronic / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012189:Retrospective Studies; D014015:Tissue Banks; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C054369:MAPT protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C556915:TMEM106B protein, human; D016875:tau Proteins
keywords: Brain bank; Chronic traumatic encephalopathy; Microtubule-associated protein tau; Sports; Traumatic brain injury