ABSTRACT

Traumatic brain injury (TBI) has been a common cause of morbidity and mortality throughout history, but has had interesting twists in the industrial era and in the world of aggressive sports or modern warfare. The American public is especially troubled by the problem of hundreds of thousands of injured veterans returning from the lengthy post9/11 campaigns and is also fearful that repeat concussions experienced in contact sports played by millions of young athletes may result in progressive neurodegenerative disease and dementia. The problem of traumatic degeneration, termed chronic traumatic encephalopathy (CTE), has been long recognized in the world of boxing, but has recently come to the forefront because of several highly publicized deaths of popular NFL protagonists. Despite extensive publicity, the real risk of CTE among amateur and professional players has not been measured or adequately characterized and notions derived from autopsy studies, although useful for understanding mechanisms, cannot give an accurate picture of the range of outcomes after repeat concussions and are limited because of ascertainment bias. It is imperative that prospective studies are designed and deployed to the problem, but such approaches will take a long time to bear

fruits in view of the long incubation time of key pathologies. Meanwhile, emphasis on molecular and cellular mechanisms of deposition of a key protein, the microtubule-associated protein tau, as well as the construction of relevant animal models, may help define cause-and-effect relationships, shed light into mechanisms, and generate ideas about biomarkers and therapeutic targets. Imports from extensive work in other degenerative tauopathies such as frontotemporal degeneration may greatly facilitate innovation in this area.