Researchers led by Boston University have taken a step forward in finding a way to diagnose the degenerative brain disease known as CTE in living people, advancing the understanding of an illness that now can only be confirmed after death.
In a study published online Wednesday in the New England Journal of Medicine, teams in Boston and Arizona report that an experimental brain scan detected elevated levels of the tangled protein called tau, a sign of CTE, in a small group of living former professional football players who exhibited thinking, mood, and memory problems.
Although further studies are needed, the findings raise hopes that such scans might someday become part of a battery of tests that would diagnose CTE — chronic traumatic encephalopathy — which has afflicted many well-known football players, including the late Patriots star Aaron Hernandez.
“It’s an important finding that will hopefully at some point lead to a diagnostic breakthrough, but we’re not there yet,” said Dr. Michael Weiner, a professor of biomedical imaging, psychiatry, and neurology at the University of California, San Francisco, who was not involved in the study.
But Dr. Marwan Sabbagh, director of the Cleveland Clinic Lou Ruvo Center for Brain Health, said that for insiders following CTE research, “This is a paper that has the ‘wow’ factor” because it “answers a lot of questions and poses a lot of questions.”
The tau clusters linked to CTE had previously been seen in scans of just one or two living people with symptoms, he said, while the new study enrolled more than two dozen.
CTE has been linked to repeated hits to the head, such as those suffered by athletes in contact sports and by military personnel. Although it’s not known how common it is, the illness has captured the public’s attention because of its devastating effects on football stars and the questions it raises about the safety of youth sports.
Currently, CTE can be diagnosed only by examining the brains of deceased victims to look for a distinctive pattern of tau deposits. Its symptoms in the living — impulsivity, mood swings, memory problems, and impaired judgment — are vague and variable, and resemble those of other illnesses.
Unless doctors can identify CTE in the living, researchers won’t be able to answer such questions as the prevalence of the disease, why CTE affects some players and not others, and what factors put a person a risk for developing it, said Robert Stern, neurology professor at the BU School of Medicine and leader of the study.
“And perhaps more importantly,” Stern added, “how can we treat and possibly even prevent CTE? The only way to really answer those types of questions is to have the ability to diagnose CTE during life.”
The new study involved 26 former National Football League players ages 40 to 69 who had symptoms that might indicate CTE.
Researchers performed two brain scans on the former players and on a control group of 31 people of similar ages but with no symptoms and no history of head injury.
One scan looked for tangles of tau, which is present in both Alzheimer’s disease and CTE.
The other scan detected amyloid plaques, a different abnormality associated with Alzheimer’s disease but not CTE.
The scans found that:
■ As a group, the former players had much more abnormal tau than the control group.
■ Only one former player had amyloid, suggesting their symptoms were probably not caused by Alzheimer’s.
■ No one in the control group had levels of tau as high as those found among some of the players.
■ Those who played the most years of football had the highest levels of tau.
The scans provided an overall finding for the group but were less revealing when it came to individuals, limiting their utility as a diagnostic tool. Some of the former players had the same levels of tau as some people in the control group, for example.
And there was no correlation between the amount of tau and the severity of symptoms.
“That was a very interesting finding,” Sabbagh of the Cleveland Clinic said. “In other brain conditions, the amount of tau correlates well with symptoms.”
Stern, the lead author, described the findings as “a really important new advance in our knowledge about diagnosing CTE during life.” But developing an effective diagnostic tool, he said, will require many more studies with more people, and the ability to examine the brains of those who die to see whether postmortem findings match what the scans showed.
The brain scans were done using positron emission tomography, or PET, a procedure that detects a radioactive substance, called a radiotracer, that is injected into the patient. Each type of radiotracer attaches to a certain molecule. In the scanning for tau, the researchers used a radiotracer that has not yet been approved by the Food and Drug Administration and is available only for research.
In other studies, researchers have been looking for abnormal amounts of tau in the blood and spinal fluid — but that could indicate illnesses other than CTE. Ultimately, Stern said, a combination of tests will probably be needed to diagnose CTE.
In addition to Stern’s BU group, the team included researchers from Harvard Medical School, Brigham and Women’s Hospital, the Veterans Affairs Boston Healthcare System, and institutions in Arizona.
The study was partly funded by Avid Radiopharmaceuticals, the company that makes the radiotracer used in the tau PET scans. Additional funding came from the National Institutes of Health and the state of Arizona.