A test for CTE in the living may be closer than ever
By Ken Belson
Chris Eitzmann seemed to excel at everything until he didn’t.
He parlayed a Harvard football captaincy into an invitation in 2000 to the New England Patriots’ training camp. After bouncing around the NFL, Eitzmann retired from pro football in 2002, got a Master of Business Administration from Dartmouth and worked at several big financial firms in Boston, where he and his wife, Mikaela, had four children.
By 2015, however, Eitzmann began a descent that has become familiar to former football players afflicted with CTE, or chronic traumatic encephalopathy, the degenerative brain disease associated with repeated blows to the head.
Eitzmann had loved mountain biking, running and lifting weights, but he quit exercising and drank to excess. After a move to Mikaela Eitzmann’s family farm back in their home state of Nebraska two years later, Chris Eitzmann’s behavior became more alarming. He would disappear for long stretches of the day and neglect his work. His drinking got worse, and she said he would sometimes drive drunk.
In December 2021, Eitzmann was found dead in his Boston apartment of alcohol poisoning at 44. Almost a year later, doctors at Boston University found that he had CTE, a disease that can still only be diagnosed posthumously. Mikaela Eitzmann said that knowing whether her husband had the disease while he was alive would have markedly changed the final years of his life.
“If he had known that it really was something, and not just this endless vacuum of not knowing, if he had an idea that he could have grabbed on to, that clarity and understanding would have been so valuable,” she said.
Without treatment options, a CTE diagnosis could provide only clarity for former players such as Chris Eitzmann who have reason to believe they may be affected. But it could eventually help current players make risk assessments about when to give up tackle football and help former players seek treatment.
Researchers are hoping that a series of recent breakthroughs will help speed up the development of a test for CTE in the living.
Currently, the only way to accurately diagnose CTE is to stain brain samples and examine them under microscopes to look for the presence of the specific tau proteins associated with CTE.
But if ongoing studies pan out, there could be a test for CTE in the living in as few as two years, according to one leading researcher. The future of testing for CTE hinges on developing ways of identifying the protein without requiring brain samples. So, scientists in multiple research institutes worldwide are working to identify biomarkers for the disease that can be seen in samples of blood, saliva or spinal fluid, or by using brain imaging scans.
Additionally, Alzheimer’s diagnostics have advanced to the point at which blood tests are now on the market, and companies that have developed those tests are now looking to create a similar blood test for CTE.
The most comprehensive effort to develop a test for CTE in the living began in 2015, when the U.S. National Institutes of Health awarded a $17 million, seven-year grant to the DIAGNOSE CTE Research Project.
As part of the wide-ranging project, doctors from the NIH are tracking 120 former NFL players, 60 former college players and 60 people with no history of repetitive head impacts to see if they show symptoms of CTE. Beginning in 2016, participants underwent a three-day examination that included neuropsychological and neurological assessments and were asked to detail their histories of brain trauma, lifestyle and other health factors, such as genetics, in a comprehensive look at their health.
The participants are undergoing follow-up exams remotely to see if they demonstrate any CTE symptoms or if those symptoms have progressed, and researchers hope that changes in their tests — which include spinal taps, blood analysis and neuroimaging scans — will help them identify biomarkers for CTE. The multidisciplinary group of 50 researchers from nearly a dozen institutions globally are already publishing some of the findings from the three-day exams.
“I now feel we are much closer to having fluid biomarkers, and in particular blood-based biomarkers, that will play an important role in diagnosing CTE in life,” said Robert Stern of Boston University, the lead investigator for the project.
The long search to identify CTE biomarkers reached a watershed moment in 2019, when a group identified that the tau proteins specific to CTE were distinct from those in Alzheimer’s disease and other tau-based neurodegenerative diseases.
Led by Michel Goedert, program leader at the Laboratory of Molecular Biology at the Medical Research Council in Cambridge, England, the group published the findings of their study, which showed that the abnormal filaments, or threads inside of cells, were observable, giving hope that their presence could be tested for via PET scans.
Positron emission tomography, or PET, scans are tests that use a radioactive compound, or radio tracer, that is injected into patients to create images of biochemical processes in the brain and other parts of the body.
Researchers have been developing radio tracers for use in studies of football players and others with head trauma to see if those tracers bind to the tau protein associated with CTE and inflammation in the brain.
“We are getting very close to advancing new radio tracers in humans to image the tau that is more prevalent in CTE,” said Neil Vasdev, a radiochemist at the University of Toronto who is developing several promising radio tracers that focus on identifying the CTE tau protein. “I like to think that we’re within two to five years, not 10 years” of developing a test for CTE in the living.
Doctors leading CTE research have for years said that a diagnostic test for the living was five to 10 years away. The expectation that the finish line is moving up marks a significant change in forecast for research that is complicated by a relatively small sample size of study participants and the need for long-range studies. But identifying tracers that can be seen on PET scans could lead to diagnosing CTE before its symptoms are apparent.
“In principle, this should make it possible to seek to diagnose these deposits at an early stage,” Goedert said. “You have to be able to identify people who have some of these deposits in their brains before they have symptoms.”
Still, doctors like Gil Rabinovici at the University of California, San Francisco, have hit stumbling blocks to employing tracer technology. Rabinovici’s work examines how one tracer, MK-6240, attaches to CTE tau in the brain of several dozen former NFL players. The signal from those radio tracers thus far has been weak.
“It is quite difficult because you don’t know if they have CTE in life, and if you use the scan, you can’t immediately say ‘aha’ and have a level of truth in the scan,” he said.
The good news, Rabinovici said, is that the tau proteins in Alzheimer’s and CTE have more similarities than differences, so researchers can use some of the same techniques for tests.
“I don’t think we need to start from scratch,” he said. “That’s where I’m cautiously optimistic we’ll find a tracer that works.”