Researchers Shed New Light on Chronic Traumatic Encephalopathy

Encephalopathy
Characteristic staining of p-Tau (green) in a case of CTE. Claudin-5 (red) protein levels are discontinuous and not present in areas of p-Tau accumulation around blood vessels. This is an indication of a dysfunctional blood brain barrier.

Working with the Dublin Brain Bank, Beaumont Hospital and St James’ Hospital, scientists at Trinity College Dublin have discovered a new and previously un-reported feature of the degenerative brain condition chronic traumatic encephalopathy (CTE) that may shed light on how it is diagnosed and ultimately treated.

CTE is a rare condition that has gained widespread attention in recent years and has been linked with repetitive mild traumatic brain injuries (mTBI), such as concussion, sustained by athletes and military personnel.

The research, just published in the leading international neuropathology journal, The Journal of Neuropathology and Experimental Neurology, presents a report of an individual diagnosed with CTE post-mortem. The scientists examined brain tissues from this individual and found a predominant vasculopathy or damage to blood vessels in the brain.

Importantly, blood vessels in the brain are unlike vessels in other areas of the body, having unique properties that tightly regulate what gets into or out of the delicate neural tissue. This is termed the blood brain barrier (BBB), and a compromised BBB has been linked to numerous other neurological disorders such as Alzheimer’s disease (AD) and Multiple Sclerosis (MS).

Commenting on the recent findings, Assistant Professor in Genetics at Trinity, Dr Matthew Campbell, said: “While this is only a case report, it provides the first ever evidence that CTE is directly associated with damage to the BBB. Additionally, the pathology we observed was similar to that seen in cases of brain trauma, suggesting a definitive link between repetitive mTBI and CTE.”

Clinical lead on an on-going study examining the role of the BBB in concussive brain injuries, Dr Colin Doherty said: “These findings are not only important for our understanding of CTE in general, but they also suggest that we can use clinical tools to determine if the BBB is damaged in-life in individuals exposed to repetitive mTBI.”

Professor Michael Farrell, consultant neuropathologist and co-Director of the Dublin Brain Bank, said: “Understanding how CTE develops will be critical to identifying new ways to detect its onset in living subjects in addition to developing therapies for this rare but socially important brain disorder.”

The work was funded in part by grants from Science Foundation Ireland, the Health Research Board of Ireland, the Bright Focus Foundation, and the St James’ Hospital Research Foundation.