THE EFFECT OF REPETITIVE MILD TRAUMATIC BRAIN INJURY ON TAU PATHOLOGY

Abstract

Mild traumatic brain injury is the most common form of concussion and is prevalent among contact sports athletes and military personnel. Repetitive mild traumatic brain injury (rmTBI) can trigger the activation of several molecular cascades that lead to neuropathological consequences in the brain. Moreover, rmTBI has been correlated to neurodegenerative diseases such as chronic traumatic encephalopathy (CTE). CTE is a slow, progressive tauopathy that exhibits neurofibrillary tangles (NFTs) accompanied by psychiatric and cognitive manifestations. NFTs are intracellular aggregates formed from the misfolding and aggregation of tau protein. A vast majority of individuals following a TBI event demonstrate early tau accumulation, independent of age, suggesting a potential pathological link between TBI and tauopathies. The role of tau aggregation in brain and in subsequent clinical symptoms following rmTBI remain to be elucidated. Moreover, effective diagnostic methods for TBI and tau pathology are lacking. The goal of the current study is to assess the generation of tau aggregates and brain pathology following rmTBI induction in mice. Thus, transgenic (Tg) tau mice were subjected to rmTBI events, which mimic multiple sub-concussive impacts in athletes, over various time-points. Tg tau mice subjected to rmTBI demonstrated neurobehavioral changes as well as early misfolded tau deposition and elevated tau levels in brain. These results indicate that rmTBI could be a trigger for early aggregated tau formation; in addition, misfolded tau can play a role in the psychiatric and cognitive behaviors affiliated to TBI and disease. Overall, this work will shed light to understanding the effect of rmTBI in relation to tau pathology and behavioral impairment and will potentially provide a potent diagnostic tool to detect tauopathy onset and monitor TBI-induced brain damage in the future.