Title: Mechanisms of traumatic brain injury and Alzheimer disease risk

Abstract

Objective: To investigate the role of traumatic brain injury (TBI) in Alzheimer disease. Introduction: The most common type of dementia; Alzheimer’s Disease (AD), and the cause of disability in young adults; TBI have credible associations but are relatively elusive, and highly complex in nature. Recently, alterations in blood brain barrier (BBB) integrity have been shown to have implications in dementing disorders. Further, downstream effects on capillaries may alter not only the behavior, but also cognitive output in the affected patient precipitating AD. Methods: PubMed and PubMed Central data bases were methodically searched for articles within the last ten years, incorporating the keywords- Alzheimer’s disease and TBI. After searching, original articles were included in the study. Results: A group of ten studies were analyzed. Briefly, Hayes et. al found that moderate to severe TBI is a stronger external risk factor for the gradual progression of AD as compared to the milder trauma. A retrospective study estimated prior history of TBI, and earlier onset of AD, and concluded that dementia occurred 2.8 years earlier in comparison to the control group (p = 0.002). Notably, one study hypothesized disruption of the glucose hemostasis in the brain that appears to be evoked by TBI relying on the premise of common mechanistic pathways. Most importantly, individuals with a genetic link to APOE ϵ4 allele have been shown to progress into AD pathophysiology over a relatively short interval following TBI insult. Conclusions: TBI does amplify the overall risk for AD. The mechanisms are multifactorial and include environmental, genetic, and cell-signaling components that partake in disease process. More likely than not, it is an injury led remodeling of the BBB that consequently triggers a cascade of reactions leading to hyperphosphorylation of the tau protein.