Last week, the family of football player Aaron Hernandez ― who hanged himself in a prison cell in April while serving a life sentence for the murder of a friend ― filed a $20 million lawsuit against the NFL and the New England Patriots. Hernandez’s last days were marked by aggression, memory loss and impulsiveness, but it was only after his death that his loved ones got some insight into why. He was given a post-mortem diagnosis of chronic traumatic encephalopathy ― a progressive brain disease linked to repetitive head trauma, the kind that can accompany rough sports, military service or abuse.
The brain of someone with CTE is marked with abnormal clumps of the tau protein in a pattern unique to the disorder. But CTE, like other neurodegenerative diseases, can only be definitively diagnosed with a brain examination after death. Brain injury experts say that if doctors had a simple, clear test that could firmly diagnose the disorder, patients and their families could have some measure of peace knowing what was causing their symptoms, and clinicians could create a treatment plan incorporating the most appropriate therapies for CTE.
Scientists are closer than ever to a test like this. Dr. Ann McKee of Boston University’s CTE Center has identified a certain protein found in brain tissue and cerebrospinal fluid. Levels of this protein are significantly higher in the brain samples and spinal fluid of people with diagnosed CTE, as opposed to people with Alzheimer’s disease or no brain disease at all.
If the finding is replicated in larger samples, doctors might be able to use spinal taps to analyze spinal fluid and diagnose CTE in living patients. This, in turn, could transform how doctors treat the condition, and give people ways to protect themselves from further damage, McKee says.
“The whole playing field changes because once there’s a way to diagnose CTE before death, we can start to evaluate different treatments to see if they’re efficacious,” she said. “If it enables us to diagnose CTE in the very earliest stages, we would be able to advise an individual on whether or not to continue in the activity that’s causing the exposure to head impacts.”
A protein in spinal fluid could one day help identify CTE
The protein in question, CCL11, is made in the choroid plexus, the part of the brain that produces cerebrospinal fluid. While increased levels of this protein are already linked to the inflammatory process and the aging process (the older you are, the more of it you have), having low or high amounts of CCL11 have also been linked to other brain diseases like Alzheimer’s, amyotrophic lateral sclerosis and Huntington’s disease.
McKee and her colleagues wanted to explore the relationship between CCL11 and CTE by comparing levels of the protein in brain specimens from football players, people with Alzheimer’s disease and people who died with healthy brains.
She analyzed brain specimens from 23 male college and professional football players who had been diagnosed with CTE after death, specimens from 50 people who’d had Alzheimer’s disease but no history of military service or contact sports, and specimens from 18 people who died without a neurodegenerative disease.
McKee found that the men with diagnosed CTE had significantly higher CCL11 levels than the people with Alzheimer’s disease or the control group.
Elevated levels of CCL11 were also found among people with CTE who had played 16 or more years of football. The more years a person played football, the higher their protein levels were. However, the researchers found no correlation between levels of CCL11 and the number of recorded concussions a player had experienced.
In a smaller group of specimens that also had spinal fluid available for analysis, researchers found that people with diagnosed CTE had higher levels of CCL11 in their spinal fluid compared to the control groups, and that these levels increased with the number of repetitive head impacts the person had sustained during their lifetime.
McKee predicts that if the CCL11 finding is validated in larger studies, it could one day serve as one of several biomarker tests, along with brain scans and body fluid tests for the tau protein, that doctors could use to diagnose CTE.
“It’s very unlikely that a single biomarker will be used to confidently diagnose CTE,” she said. “It’s most likely that it will be a panel of biomarkers.”
How CTE diagnostic tests could improve patient care
Biomarker tests to diagnose CTE would be a game changer for patients and their families, because “knowing is half the battle,” said Dr. David Merrill, an assistant clinical professor of psychiatry and biobehavioral sciences at the University of California, Los Angeles.
“A confident clinical diagnosis would give patients and family firm understanding of why the dramatic mood, cognitive, and behavioral changes are happening,” said Merrill, who was not involved in McKee’s research but is exploring how to use MRI scans to diagnose CTE. “A clear organic/biologic diagnosis disarms the sometimes automatic, but inaccurate, presumptions about laziness, personality, or lack of willpower.”
In particular, the idea of a fluid biomarker test is exciting to CTE researchers because it would be less expensive than imaging tests and brain scans that require patients to be exposed to low levels of radiation. The need for an alternative to brain scans is especially relevant for football players, Merrill noted.
“Football players can be too large for conventional scanners, or have metal implants or devices that make MRI problematic or more complicated,” he said.
If researchers close in on a potential test for CTE, it could further scientific knowledge about the condition and point the way toward a cure, said Dr. Anthony Alessi, an associate clinical professor of neurology and orthopedics at UConn Health. However, there’s still a long way to go before doctors would be able to use such a test with confidence, as any test results scientists get today would need to be confirmed by a post-mortem diagnosis, potentially years later.
Alessi also voiced concerns about how a CTE test might change the way doctors approach treatment and care.
“If there’s a football player or an athlete or a boxer, and they’re telling me they have memory loss or explosive behavior, I’m still getting them into therapy” — whether or not a test confirms CTE, he said. A CTE test could also have a negative effect on people, he said, as it could make someone believe they will definitely develop dementia even when that may not be the case.
McKee acknowledges that a doctor’s job is to take care of a patient, not a test result. But the ability to make a CTE diagnosis during a patient’s life could help offer clues about what the patient can expect down the road, and guide researchers on specific targets for treatment. Currently, there is no cure for CTE, just as there is no cure for Alzheimer’s disease.
Because CTE is so difficult to diagnose, there is no way of estimating how many people in the U.S. may have it. In 2016, McKee analyzed 111 brains of former NFL players and found that all but one showed signs of CTE. However, this group was not random and didn’t constitute a representative sample of all NFL players, as many of these brain specimens were donated by family members specifically because they suspected CTE had played a role in the person’s demise.