Diagnosing CTE: A Breakthrough Could Be Here ‘In the Next Five Years’

Soon, researchers could have a way to diagnose CTE in living patients. What it would mean if football players, mid-career, could test themselves for the disease

In the more than a decade since the first case of chronic traumatic encephalopathy (CTE) was reported in a former NFL player, the neurodegenerative disease has been both the sport’s greatest threat and biggest mystery. Former players openly wonder if they have CTE. Current players ponder the risk-benefit of continuing to play. Parents of future players want to know what the odds of long-term health issues are if they sign their kid up for football.

A new discovery by researchers at Boston University’s School of Medicine may be a breakthrough toward a game-changer for America’s most popular game: The ability to diagnose CTE in living patients, something that is not yet possible.

“I am pretty optimistic we will have a test, or maybe a series of tests, that are diagnostic for CTE during life, and I think that will happen in the next five years,” says Ann McKee, the neuropathologist who is the director of BU’s CTE Center and senior author on the study. “We are making a lot of progress. We know a lot more about this disease than when we started, and we are starting to tease out the important markers and pathways that are involved.”

This is a goal that scientists have been racing toward, and that those with a stake in football have been anticipating with apprehension. Even the NFL has acknowledged a link between CTE and the repeated head trauma native to football, but for now the disease remains something uncertain and far off in the future to current players. A test for it in the living would change that.

A study published Tuesday in the science journal PLOS ONE appears to be a significant step toward that. The BU researchers identified a potential diagnostic biomarker for CTE, CCL11, a protein that was found in increased levels in the brain tissue and cerebrospinal fluid of 23 American football players who had been diagnosed with CTE after death—18 NFL players, one CFL player and four college players. Those levels were compared against two other groups: 50 subjects diagnosed with Alzheimer’s who did not have a history of head trauma, and 18 non-athlete controls. Researchers also found significantly higher levels of the protein among subjects with more than 16 years of football experience, when compared to those with less.

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More work is needed to confirm these preliminary findings; most critically, this research was done in post-mortem samples. The next step for the researchers is to confirm these findings in living patients with a history of repetitive head trauma, compared to those without. They need to continue to test a larger number of subjects, including a useful control group that was not included in this study—a group of athletes who do not have CTE.

If wider studies do, in fact, confirm that CCL11 can be used as a specific in vivo marker for CTE, then what? The goal is for multiple biomarkers like this one to be part of a test for CTE that could be conducted, say, during a doctor’s visit. A sample of spinal fluid would be collected through a spinal tap, or if the marker (or markers) is found to be present in the bloodstream as well, drawing a blood sample would be even easier. A laboratory assay would then be performed on the spinal fluid or blood sample to measure the level of the biomarker and determine whether or not it is in the range that indicates CTE.

There’s been a major push to understand CTE ever since Bennet Omalu, then a forensic neuropathologist for the Allegheny County Coroner’s office, discovered it in the brain of Mike Webster during his autopsy in 2002. Much is still yet to be known. Just two years ago, researchers met for the first time to define the specific criteria by which it should be diagnosed in post-mortem exams, and scientists are still trying to unlock how, and to what extent, this neuropathology causes clinical symptoms.

The identification of a possible biomarker presents the opportunity not just for diagnosis in living patients, but also to decipher how the disease progresses over time and thus develop potential treatment options. (Right now, there are none). The CCL11 biomarker is associated with neuroinflammation, one of the symptoms of traumatic brain injury that is believed to abet the progression of abnormal Tau build-up and neurodegeneration. McKee said in this study they saw elevated levels of the biomarker in both mild and more severe cases of CTE, opening the door to early diagnosis and intervention. After years of cutting open brains and assessing the damage, she said, this was her first optimistic finding.

Earlier this year, McKee was an author on a sobering paper published by the BU group in The Journal of the American Medical Association, presenting their findings of CTE in 110 of the 111 deceased NFL players whose brains they examined. The sample was largely composed of brains donated because these players had shown some symptoms of neurological impairment while alive—but the numbers were alarming nonetheless. Last week, she added another diagnosis, that Aaron Hernandez, the former Patriots tight end who killed himself earlier this year at age 27 while incarcerated on a murder conviction, had a severe form of CTE.

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This study keeps hope alive that CTE will, in the not-too-distant future, no longer be a retrospective diagnosis. Instead, people who have been exposed to head trauma, including current players, could be tested while there is still time to intervene—whether by some form of treatment, or walking away from the sport. “Without information, we can’t do anything about this; it’s just a problem,” McKee said. “But I think this is part of the solution.”

For the sport of football, it would be a watershed moment to have answers to questions like, How many people have CTE? What are the risk factors that make some people more or less likely to develop it? And, especially: Do I have CTE? This would be different from, say, a genetic test that tells you whether or not you are at risk for a certain disease down the line; it would, in theory, tell you if there are already changes underway in your brain. This would also present another, more philosophical question: Do you want to know?

An era in which there are answers to those questions might not be far away—and there would be no turning back.

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