Alzheimer's disease and chronic traumatic encephalopathy: Distinct but possibly overlapping disease entities

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Background—Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE) have long been recognized as sharing some similar neuropathological features, mainly the presence of neurofibrilary tangles and hyperphosphorylated tau, but have generally been described as distinct entities. Evidence indicates that neurotrauma increases the risk of developing dementia and accelerates the progression of disease. Findings are emerging that CTE and AD may be present in the same patients. Clinical presentation—We present a series of previously unpublished cases with one case demonstrating possible neurotrauma-related AD, one pure CTE, and an example of a case exhibiting features of both AD and CTE. The future significance of this work lies not only in the confirmation of AD-CTE coexistence but more importantly, ways of generating a hypothesis about the possibility that CTE may accelerate AD development. Understanding the relationship between neurotrauma and neurodegenerative disease, will help elucidate how distinct disease entities can co-exist in the same patient. It will ultimately require the use of preclinical animal models and repeat injury paradigms to investigate clinically relevant injury mechanisms. These models should produce a CTE-like phenotype that must be both neuropathologically and behaviorally similar to human disease. Conclusion—In this case series and review of the literature, we present a discussion of AD and CTE in the context of neurotrauma. We highlight recent work from repetitive neurotrauma models with an emphasis on those exhibiting a CTE-like phenotype. We briefly address potential mechanisms of interest shared amongst AD and CTE and advocate for future experiments to enhance understanding of CTE pathophysiology and the relationship between CTE and AD.