AbstractDementia pugilistica (DP) is associated with chronic traumatic brain injury (CTBI), and leads to a “punch drunk” syndrome characterized by impairments in memory and executive function, behavioral changes, and motor signs. Microscopic features include the accumulation of neurofibrillary tangles (NFTs), beta-amyloid (Aβ), and TAR DNA binding protein 43 (TDP-43) pathology. Here we describe detailed clinical and neuropathological data about a 55-year-old retired boxer (ApoE3/4), who presented with executive dysfunction and behavioral impairments. At autopsy, significant Aβ pathology was seen, primarily in the form of diffuse plaques. Tau pathology was extensive and was determined to be of Braak and Braak stage VI. Frontal white matter showed evidence of glial tau inclusions (astrocytes and oligodendroglia). Cerebrovascular pathology was minimal with patchy amyloid angiopathy. Inflammation was another key feature, including microglial activation and significant C1q labeling of neurons, along with NFTs. TDP-43-positive pathology was also observed. Inflammation may be a key inciting as well as propagating feature of DP neuropathology.