Background: It has been asserted that Chronic traumatic encephalopathy (CTE) pathology is only present in former athletes and others who have been exposed to repetitive concussions, subconcussive blows, or both. However, researchers have recently reported that similar pathology is also present in people who have now known exposure to repetitive neurotrauma. We hypothesized that CTE pathology would be present in men who had no known history of repetitive neurotrauma. Methods: Comprehensive medical record reviews and health surveys completed by a family member were completed for the eight men in this case series. Post-mortem tissue from multiple brain regions was immunostained for hyperphosphorylated tau (p-tau) to assess for CTE pathology, Braak stage, and aging-related p-tau. Tissue was immunostained for amyloid-β to approximate Thal amyloid phase and CERAD plaque score. The National Institute on Aging-Alzheimer's Association 2012 consensus recommendations for Alzheimer’s disease neuropathologic changes were used. TDP-43 immunohistochemistry was performed on medial temporal lobe including hippocampus. Amyloid-beta precursor protein and neurofilament protein immunostains were performed to evaluate for possible axonal trauma. Alpha-synuclein immunostains were performed to rule out synucleinopathy. Basal ganglia were stained with the Prussian blue reaction for iron. Results: Six of the eight cases (i.e., 75%) showed p-tau in neurons, astrocytes, and cell processes around small blood vessels in an irregular pattern at the depths of the cortical sulci. The changes were focal and limited in terms of overall extent. Two of the eight cases had a history of traumatic brain injury and one of them showed CTE pathology. Five of the six cases (83%) with no known history of neurotrauma met consensus criteria for CTE. Conclusion: This study adds to the emerging literature indicating that CTE pathology (or CTE-like pathology) is present in people not known to have experienced multiple concussions or subconcussive blows to the head.

Mild Chronic Traumatic Encephalopathy Neuropathology in People with No Known Participation in Contact Sports or History of Repetitive Neurotrauma