After examining the brains of former professional football players, researchers might be a step closer to diagnosing the devastating brain disease chronic traumatic encephalopathy in the living, according to a study published Wednesday in the New England Journal of Medicine.
The researchers utilized PET imaging to find tau, an abnormal protein that’s a signature indicator of CTE, using a radioactive drug or tracer called flortaucipir. The researchers imaged the brains of 26 living former football players and compared them with the brains of 31 people with no history of traumatic brain injury.
The brains of the former players were more likely to light up and signal tau deposits than those of people who hadn’t had a brain injury. Furthermore, the scans detected tau in the same regions where tau has posthumously been found in CTE-diseased brains.
“This is an important next step, but it doesn’t mean we have the answer yet,” said lead study author Robert Stern, director of clinical research for Boston University’s Chronic Traumatic Encephalopathy Center.
CTE was discovered in the brain of a former football player, Pittsburgh Steelers center Mike Webster, during an autopsy in 2002. In the 17 years since, over 100 former National Football League players have been diagnosed with the neurodegenerative disease, along with other athletes, military veterans and victims of abuse, after their deaths. Yet there is still no way to diagnose it in the living.
Looking inside the brain
Previous studies have used other tracers to attempt to image tau, but those agents weren’t as specific in distinguishing tau from beta amyloid, the protein that signifies Alzheimer’s disease.
“The newer-generation tracers are much more specific for tau,” said Neil Vasdev, director of the Azrieli Centre for Neuro-Radiochemistry. Vasdev was not directly involved in the study analysis but helped the research team set up the radiochemistry protocol used in the centers that conducted the study.
Scientists believe that CTE results from repeated head trauma. In football, this can happen not just from hard hits to the head that result in concussion but from the constant rattling of the brain inside the skull that occurs during tackles and other plays. These repeated hits are known as subconcussive hits and can result in a buildup of tau.
CTE develops when the protein begins clumping around small blood vessels and in the valley of the cortex. From there, the protein spreads and destroys other parts of the brain. There is no cure for CTE.
The neurodegenerative disease results in Alzheimer’s-like symptoms including mood swings, memory loss and impulsive behavior. As the disease progresses, it can also lead to paranoia, dementia and suicidal thoughts.
For the new study to evaluate the connection between tau and the players’ potential behavioral and cognitive symptoms, the researchers gave all the participants tests that assessed executive function, mood and memory. The researchers did not identify the former players involved in the study.
Stern and his colleagues found that there wasn’t an association between how much tau was detected and the players’ test scores, but the more years played, the higher the amount of tau deposition in the brain.
A step forward
To confirm that the symptoms that players reported weren’t related to Alzheimer’s, the researchers also imaged the participants for beta amyloid proteins using florbetapir, one of the most widely used imaging tracers. Researchers found that the former players had similar levels of beta amyloid proteins as the control group.
The players involved in the study were males between the ages of 40 and 69 who had played in the NFL for at least two years and played a minimum 12 years total of tackle football. Quarterbacks, kickers, special teams players and players who had reported a traumatic brain injury in the prior year were excluded from the study.
The study was funded in part by Avid Radiopharmaceuticals, a subsidiary of Eli Lilly and maker of the two tracer agents used in the research.
Despite the relatively small numbers of players tested, Vasdev believes that the findings could have long-lasting implications.
“It’s really that first step that will generate more scientific data and discussions around diagnostics and treatment options or management options for patients suffering from traumatic brain injuries,” he said.
The 26 players who Stern and his colleagues evaluated make up the largest group to date using this method to signal tau. But there are still a number of questions to be answered. Why does the disease progress more severely in some than in others? Why do some people develop the disease at all?
Within the next five years, Stern believes, scientists will have a meaningful way to diagnose CTE in the living. He and his colleagues are further analyzing a larger sample of players to help get there. “We can refine our ways of analyzing this tracer in this larger sample and hopefully move this field even further,” he said.
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Stern has been vocal about his concerns about links between football and CTE, testifying before Congress in 2014 and 2017 about the dangers of repeated head trauma. A 2016 congressional report found that when the NFL learned that Stern’s research proposal had been selected by the National Institutes of Health as part of a NIH-NFL grant partnership, the NFL tried to pull its funding. Ultimately, the National Institutes of Health funded Stern’s work.
Stern is cautious but optimistic about the results of this study.
“This is an exciting scientific finding,” he said. “It doesn’t mean we are there yet. Lots more work needs to be done.”
Correction: A previous version of this story gave an incorrect age range for the participants.