Bieniek Kevin F, Ross Owen A, Cormier Kerry A, Walton Ronald L, Soto-Ortolaza Alexandra, Johnston Amelia E, DeSaro Pamela, Boylan Kevin B, Graff-Radford Neill R, Wszolek Zbigniew K, Rademakers Rosa, Boeve Bradley F, McKee Ann C, Dickson Dennis W
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.
Acta Neuropathol. 2015 Dec;130(6):877-89. doi: 10.1007/s00401-015-1502-4. Epub 2015 Oct 30.
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.
慢性创伤性脑病（CTE）是一种与重复性创伤性脑损伤（TBI）相关的进行性神经退行性疾病，其特征是在脑沟深处出现过度磷酸化tau蛋白沉积。我们试图在一个神经退行性疾病脑库中确定有或没有接触性运动参与史的个体中CTE病理情况。回顾了1721名男性的现有病历，以寻找过去受伤或参与接触性运动的证据。随后，对有运动暴露记录史的病例以及年龄和疾病匹配的无此类暴露的男性和女性的大脑皮质样本进行tau免疫组织化学处理。对于有可用冷冻组织的病例，对载脂蛋白E（APOE）、微管相关蛋白tau（MAPT）和跨膜蛋白106B（TMEM106B）的变异进行基因分析。免疫组织化学显示，66名前运动员中有21人具有与CTE一致的皮质tau病理。在198名未接触过接触性运动的个体中未检测到CTE病理，其中包括33名有记录的因跌倒、机动车事故、家庭暴力或袭击导致的单次TBI个体。在接触过接触性运动的个体中，有CTE病理的个体与无CTE病理的个体在 noted临床病理特征方面没有差异。有CTE病理的个体在基因变异方面没有显著差异，但我们观察到MAPT H1单倍型略有增加，与无CTE病理的个体相比，有运动暴露和CTE病理的个体中保护性TMEM106B rs3173615次要等位基因的纯合携带者往往较少。总之，本研究确定了一小部分但具有显著意义的患有神经退行性疾病并伴有CTE病理的个体。CTE病理仅在有记录参与接触性运动的个体中检测到。接触接触性运动是CTE病理的最大风险因素。需要进一步研究CTE病理的临床相关性。
