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Clinical presentation: This study presents a series of previously unpublished cases, with one case demonstrating possible neurotrauma-related AD, one pure CTE, and an example of a case exhibiting features of both AD and CTE.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 co-existence, 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 pre-clinical 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 behaviourally similar to human disease.

Conclusion: This case series and review of the literature presents a discussion of AD and CTE in the context of neurotrauma. It highlights recent work from repetitive neurotrauma models with an emphasis on those exhibiting a CTE-like phenotype. Potential mechanisms of interest shared amongst AD and CTE are briefly addressed and future experiments are advocated for to enhance understanding of CTE pathophysiology and the relationship between CTE and AD.

Keywords:

• Alzheimer’s disease
• chronic traumatic encephalopathy
• dementia
• neurotrauma
• traumatic brain injury

Declaration of interest

An American Medical Association Foundation Seed Grant, American Association of Pharmaceutical Scientists Pre-Doctoral Fellowship, American Foundation of Pharmaceutical Education Pre-doctoral Fellowship and a Neurosurgery Research and Education Foundation Medical Student Summer Research Fellowship were awarded to support Brandon Lucke-Wold. Ryan Turner was supported by a NIH Training Grant.

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.