Researchers Find CTE in 345 of 376 Former NFL Players Studied

The Boston University CTE Center announced today that they have now diagnosed 345 former NFL players with chronic traumatic encephalopathy (CTE) out of 376 former players studied (91.7 percent). Among those diagnosed in the last year are two former players who once represented the teams paired in this Sunday’s Super Bowl LVII matchup – former Philadelphia Eagles quarterback Rick Arrington, who played three seasons for the Eagles from 1970-73, and former Kansas City Chiefs defensive tackle Ed Lothamer, who played for the Chiefs in the very first Super Bowl and was a member of their winning team in Super Bowl IV.

For comparison, a 2018 Boston University study of 164 brains of men and women donated to the Framingham Heart Study found that only 1 of 164 (0.6 percent) had CTE. The lone CTE case was a former college football player. The extremely low population rate of CTE is in line with similar studies from brain banks in Austria, Australia and Brazil.

The NFL player data should not be interpreted to suggest that 91.7 percent of all current and former NFL players have CTE, as brain bank samples are subject to selection biases. The prevalence of CTE among NFL players is unknown as CTE can only be definitively diagnosed after death. Repetitive head impacts appear to be the chief risk factor for CTE, which is characterized by misfolded tau protein that is unlike changes observed from aging, Alzheimer’s disease, or any other brain disease.

“While the most tragic outcomes in individuals with CTE grab headlines, we want to remind people at risk for CTE that those experiences are in the minority,” said Ann McKee, MD, director of the BU CTE Center and chief of neuropathology at VA Boston Healthcare System. “Your symptoms, whether or not they are related to CTE, likely can be treated, and you should seek medical care. Our clinical team has had success treating former football players with mid-life mental health and other symptoms.”

McKee and her team are inviting former athletes, including women, to participate in research studies designed to learn how to diagnose and treat CTE. The BU CTE Center is collaborating with its education and advocacy partner the Concussion Legacy Foundation (CLF) to recruit former football players and other contact sport athletes to five active clinical studies.

One of the studies, Project S.A.V.E., is recruiting men and women ages 50 or older who played 5+ years of a contact sport, including American football, ice hockey, soccer, lacrosse, boxing, full contact martial arts, rugby and wrestling.

S.A.V.E. stands for Study of Axonal and Vascular Effects from repetitive head impacts. The major goal is to determine how repeated head impacts from playing contact sports can lead to long-term thinking, memory and mood problems. The results could highlight strategies to treat and prevent symptoms associated with head impacts from contact sports. To learn more about Project S.A.V.E. and four other studies enrolling participants, click here. To sign up for future clinical studies, enroll in the CLF research registry.

In addition, patients and families who believe they or a loved one has symptoms that may be related to prior concussions or CTE are encouraged to reach out to the CLF HelpLine, which provides referrals to doctors and care providers, educational resources, one-on-one peer support, and monthly online support groups.

“I miss my hero dearly,” said Jill Arrington, Rick Arrington’s daughter and former CBS/FOX/ESPN sideline reporter. “It pains me to know his life was cut short by the sport he loved most. As a brain donor, part of his legacy is in this research, and I want all former football players to know how important it is to contribute and sign-up for studies so Boston University CTE Center researchers and their collaborators around the world can learn how to treat, and one day cure, the disease that devastated our family.”

Research on CTE has advanced considerably over the past five years, and the BU CTE Center soon will publish its 182nd study on CTE. In part because of advances in research on CTE, in October 2022 the National Institutes of Neurological Disorders and Stroke (NINDS), a branch of the National Institutes of Health (NIH), updated their position on what causes CTE: “CTE is a delayed neurodegenerative disorder that was initially identified in postmortem brains and, research-to-date suggests, is caused in part by repeated traumatic brain injuries.”

“We’d like to thank our 1,330 donor families for teaching us what we now know about CTE, and our team and collaborators around the world working to advance diagnostics and treatments for CTE,” McKee said.

https://www.bumc.bu.edu/busm/2023/03/06/age-of-first-exposure-to-tackle-football-and-years-played-associated-with-less-white-matter-in-brain/

CTE is a progressive neurodegenerative disease frequently found in contact sports athletes. However, many former contact sports athletes suffer from thinking problems and impulsive behavior in the absence of CTE, or with very mild CTE. This new study suggests that a separate type of brain damage, which can appear earlier than CTE, may underlie some of these symptoms.

“Damage to the white matter may help explain why football players appear more likely to develop cognitive and behavioral problems later in life, even in the absence of CTE,” said corresponding author Thor Stein, MD, PhD, a neuropathologist at VA Boston Healthcare System and assistant professor of pathology and laboratory medicine at Boston University Chobanian & Avedisian School of Medicine.

The researchers studied the brains of 205 deceased American football players donated to the Veterans Affairs-Boston University-Concussion Legacy Foundation (VA-BU-CLF) Brain Bank and measured levels of myelin, a component of white matter that covers, protects and speeds up the connections in the brain. They then interviewed family members on measures of cognition and impulsivity and then compared how career length and age of beginning tackle football related to levels of myelin, and how myelin levels related to cognition and impulsivity. In addition to more years of football played, the researchers found that starting tackle football at a younger age was also related to more white matter loss, independent of career length.

https://www.bumc.bu.edu/busm/2023/03/13/early-cte-disease-process-mechanistically-different-than-what-occurs-in-late-stages/

The brains of people who die with CTE are marked by the accumulation of a protein called tau, the same protein found to aggregate in Alzheimer’s disease (AD) brain. The amount of tau pathology in CTE correlates with severity of disease, where early-stage brains have very little pathology and late stage show severe, widespread involvement. The amount of RHI exposure, which for athletes can be measured in terms of the number of years they played a violent sport, as well as genetic risk variants influence the extent of tau pathology and associated disease severity. However, the molecular and genetic mechanisms that underly the development disease, and to what extent those effects are consistent throughout disease progression, are poorly understood.

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The researchers generated gene expression data for each individual and then performed bioinformatic and statistical analyses of the different subsets of these samples to look for gene expression patterns that are associated with different clinical, histological and genetic markers that are relevant to CTE. They then identified genes and biological processes associated with total years of play as a measure of exposure, amount of tau pathology present at time of death, and the presence of APOE and TMEM106B risk variants.

The researchers found substantial gene expression changes were associated with severe disease for most of these factors, primarily implicating diverse, strongly involved neuro-inflammatory and neuro-immune processes. In contrast, low pathology groups had many fewer gene expression changes and neuroimmune or inflammatory processes implicated and showed striking differences for some factors when compared with severe disease.

According to the researchers, if the active disease process in early disease differs substantially from late-stage disease, this could have important implications for both diagnostic and therapeutic targets. “This might explain why therapeutic targets identified from late-stage human tissue have largely failed to influence disease progression in clinical trials for many neurodegenerative diseases. In addition, if there are distinct markers of early disease progression that are absent in late disease, this would provide an opportunity to explore different diagnostics and biomarkers that we otherwise wouldn’t know to look for,” explained co-corresponding author Thor Stein, MD, PhD, a neuropathologist at VA Boston Healthcare System and associate professor of pathology and laboratory medicine.

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