Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive head injury (RHI). Recently a consensus on preliminary diagnostic criteria for CTE was reached, involving hyperphosphorylated tau at the base of the cortical sulci. With access to 24 boxers from the archival Corsellis collection I audited the boxers using the preliminary criteria. I hypothesised that the diagnostic criteria would be identified in all cases. Results indicated that 9 of the 24 boxers met a diagnosis of CTE, with 8 boxers receiving no neuropathological diagnosis.

As CTE and vascular disruption have both been associated with RHI, I sought to investigate components of the cerebral vasculature in boxers with CTE. I hypothesised that tau would be associated with an increase in vascular permeability and loss of functioning of the glia limitans. Our findings revealed focal vascular pathology, including collagenous disruption, altered gliovascular unit (GVU) permeability, gliosis and glia limitans disruption in individuals with CTE, in regions with and without tau deposition.

Aging related tau-astrogliopathy (ARTAG) is a tauopathy associated with advanced age, characterised by perivascular astrocytic tau, which appears strikingly similar to CTE. I hypothesised that since both disorders shared similar tau pathology, they would display similar GVU disruptions. Results indicated that though ARTAG tau was associated with mild GVU dysfunction, including increased GVU permeability, gliosis and integrin pathology, these findings did not match CTE GVU pathology.

Lastly, as vascular disruption was associated with CTE, early changes in cellular components of the GVU in response to trauma may aid us in understanding the aetiology of these changes. I hypothesised that pathology in the rat controlled cortical impact (CCI) model would reveal similar GVU pathology to our CTE cohort. A systematic investigation of the GVU in the CCI model revealed focal vascular compromise at the impact site. Findings revealed similar results to those seen in CTE, indicating that trauma may initiate vascular compromise in CTE.

These data suggest that vascular compromise may play an integral part in the aetiology and progression of CTE pathology and demand to be considered in addition to tau pathology when attempting to establish clinicopathological correlations.