Chronic traumatic encephalopathy (CTE)
Chronic traumatic encephalopathy (or ‘CTE’) is an organic neurodegenerative disease of the brain caused by prior substantial exposure to repetitive head impacts (‘RHI’). This underlying disease clinically manifests as a progressive neurological disorder, called ‘traumatic encephalopathy syndrome’ (TES), which is characterized by cognitive impairment (i.e., episodic memory loss, attention deficits, impaired executive functioning, language dysfunction or visuospatial perceptual changes) and/or behavioral dysregulation (i.e., socially inappropriate, disinhibited, aggressive, violent, explosive, or impulsive). The origin of TES and CTE dates back to 1927 with early descriptions of a condition called “punch drunk” in amateur and professional boxers by Dr. Harrison Stanford Martland (also called “dementia pugilistica” by Lieutenant J.A. Millspaugh ten years later), followed by descriptions of neuropathology by Dr. J.A.N. Corsellis and others (Drs. Brandenburg, Brierley, Grahmann, Hallervorden, and Ule) in the 1950s. Recognition of CTE in the brains of other contact sport athletes, notably professional football players and wrestlers, by Drs. Bennet Omalu, Ann McKee and others in 2009-2010 brought significant public and scientific interest and focus to this disease. Today, scientific research continues to explore the root causes of CTE, the disease mechanisms between head trauma and neurodegeneration, biomarkers to detect and monitor CTE in patients, and therapeutic targets to ameliorate or prevent its insidious progression.
One question that has been central to our research mission is “How common/uncommon is CTE?” While small case report and case series studies had described CTE in professional athletes, we’ve recognized that there are many more youth and amateur athletes that engage in these same contact sports, and wondered what the CTE risk was in these individuals. Beginning in 2013, we combed through the Mayo Clinic Brain Bank to identify 66 brain autopsies with clinical records describing past contact sports participation. Of those 66 former athletes, 21 had pathology in their brains consistent with CTE (32%). CTE pathology was not observed in 198 age-matched controls (including 33 autopsied with incidental traumatic brain injuries). This study was also one of the first to explore genetic factors that either increased or decreased the risk of CTE, including APOE, MAPT, and TMEM106B.
To learn more, check out our 2015 Acta Neuropathologica study!
From our Acta Neuropathologica study, we recognized two important study design limitations: 1) contact sports participation records were not frequently documented in medical records and 2) asking this study question in a brain bank cohort enriches for cases with dementia and neurodegeneration (“selection bias”). To expand on our initial efforts, we turned to the Mayo Clinic Tissue Registry and Rochester Epidemiology Project as a source of autopsy tissue outside the immediate focus of a neurodegenerative disorders brain bank. Starting with 2,566 autopsies, we used historical obituaries and high school yearbooks as a primary source of contact sport participation data. Having identified 300 former contact sport athletes and 450 non-athletes, we discovered roughly 6% of autopsies had CTE pathology or pathology suggestive of CTE. CTE pathology was more frequent in athletes than non-athletes, and mostly commonly observed in former American football players. Cases with CTE pathology were more likely to have a clinical diagnosis of dementia, psychosis, movement disorders and alcohol abuse compared to non-CTE cases. Importantly, this study explored the lower limits of CTE diagnostic criteria (“Features of CTE”) to help establish what can and what cannot be called CTE neuropathologically.
To learn more, check out our 2020 Brain Pathology study!
With different neuropathologists describing CTE pathologic features dating back to the 1950s, it is critical for the field to have a common/shared language or definition of what CTE pathology is. Dr. Bieniek has helped contribute to the first and second consensus criteria initiatives, sponsored by the National Institute of Neurological Disorders and Stroke as well as the National Institute of Biomedical Imaging and Bioengineering, to define CTE pathology. From these efforts, CTE neuropathological diagnosis consists of:
an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern.
These committees have additionally put forth recommendations on how to sample, screen and assess CTE severity with neuropathology guidelines and evaluation protocols.
Our laboratory continues to study CTE neuropathology as it relates to the clinical phenotypes, neurotrauma exposure histories, genetic disease modifiers, and co-pathologies of the human brain. We are involved in multi-institutional research efforts (with colleagues at Boston University, Mayo Clinic and other research institutions), including DIAGNOSE-CTE II and ART-AD, aimed at assessing tau pathology in relation to RHI and brain aging. Through these efforts and other laboratory projects, we hope to improve our biomedical capability to detect and treat RHI and traumatic brain injuries (broadly) in an effort to prevent CTE pathogenesis.