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

Abstract

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 Clinical presentation We present a series of previously unpublished cases with one case demonstrating possible neurotrauma-related AD, one pure CTE, and an example of a case exhibiting features of both AD and CTE.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.

Endoplasmic Reticulum Stress Modulation as a Target for Ameliorating Effects of Blast Induced Traumatic Brain Injury

“…6 We expanded upon these findings showing that TBI can contribute to tauopathy leading to CTE, Alzheimer's disease (AD), or, in rare cases, CTE/ AD. 7 Hyperphosphorylated tau aggregates around venules and begins to form oligomers and neurofibrillary tangles. We recently showed that this perivascular tau was associated with an increase in endoplasmic reticulum (ER) stress activation.…”

Disordered APP metabolism and neurovasculature in trauma and aging: Combined risks for chronic neurodegenerative disorders

“…The incidence of Aβ plaques after rmTBI may be greater, because not all who suffer rmTBI develop CTE. Collectively, these observations demonstrate overlap in the pathology of severe TBI, rmTBI (including CTE), and AD, and emphasize that polypathology, rather than just tauopathy or amyloidopathy, more accurately underlies the chronic neuropathological course of TBI (Turner et al, 2016; Washington et al, 2016). In this regard, evidence is emerging that other proteins, such as alpha-synuclein and TDP-43, can accumulate in the brain after TBI (Crane et al, 2016; Johnson et al, 2011; McKee et al, 2010).…”

Role of Tau Acetylation in Alzheimer’s Disease and Chronic Traumatic Encephalopathy: The Way Forward for Successful Treatment

“…Our group and others have shown that looking earlier in the disease process may be more valuable in finding a treatment solution that can be clinically successful. Secondary injury mechanisms such as oxidative stress, endoplasmic reticulum (ER) stress, and neuroinflammation play a more important role in disease onset than previously assumed [1][2][3][4]. These secondary injury mechanisms can be primed by genetic predisposition and triggered by insults such as neurotrauma, drug abuse, and cardiovascular disease [5][6][7].…”