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.

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Acknowledgments

We would like to thank the patients and their families. Without their generous donation, these studies would not be possible. We would also like to thank Monica Castanedes-Casey, Virginia Philips, and Linda Rousseau for their neurohistologic assistance, Michael DeTure for brain banking, and Deann Gibson for coordination of brain donations. This study was supported by the National Institute of Health (NIH) P50 NS072187 (OAR, ZKW, RR, DWD), R01 NS076471 (RR), R01 NS078086 (OAR), UO1 NS086659-01 (ACM), P30 AG13846 (ACM; supplement 0572063345-5). Other support included an unrestricted gift from Carl Edward Bolch Jr. and Susan Bass Bolch (ZKW), Department of Veterans Affairs (ACM), Veterans Affairs Biorepository CSP 501 (ACM), Sports Legacy Institute (ACM), National Operating Committee on Standards for Athletic Equipment (ACM), the National Football League (ACM), the Andlinger Foundation (ACM), and the WWE (ACM).

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Correspondence to Dennis W. Dickson.

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Bieniek, K.F., Ross, O.A., Cormier, K.A. et al. Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank. Acta Neuropathol 130, 877–889 (2015). https://doi.org/10.1007/s00401-015-1502-4

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Keywords

  • Chronic traumatic encephalopathy
  • Traumatic brain injury
  • Sports
  • Microtubule-associated protein tau
  • Brain bank