Numerous studies have elucidated the association of traumatic brain injury (TBI) incidence and progression to chronic traumatic encephalopathy (CTE) through biological markers of brain injury and degeneration in the form of pathological and gross anatomical changes. Such biological alterations observed in CTE coincide with neuropathology described in neurodegenerative diseases, such as Alzheimer’s disease (AD). This review explores the current and existing literature for established gross anatomical and pathophysiological hallmarks of CTE and compares those to changes of the human brain occurring throughout the course of AD. Of further mention are the biological and genetic markers associated with both CTE and AD. The aim of this review is to provide a sound foundation with which a comparative anatomical and pathological analysis between CTE and AD can be established, and for individuals with a genetic predisposition or a history of TBI, a common therapeutic rationale for long-term prevention can be proposed.