The Race to Develop a CTE Test for Football Players—While They Are Still Alive

Retired football players are arriving in neurology clinics carrying histories that no scan can fully capture. For years, they absorbed collision after collision. Some hits were diagnosed as concussions, but many more caused no obvious symptoms and left no clinical record.

Now, as these athletes enter middle age, some struggle to remember words or appointments, or lose the thread of conversations. Their families may notice that they seem different. They want to know whether years of head impacts are finally catching up with them.

Doctors can test their memory, scan their brain, and search for Alzheimer’s disease, sleep disorders, depression, and other explanations. But they still cannot answer the question many former players most want resolved: whether they have chronic traumatic encephalopathy, or CTE.

“At this point, we can’t diagnose CTE during life,” says Daniel Daneshvar, a physician-scientist at Mass General Brigham and Harvard Medical School who treats former athletes. “We can’t do it with known certainty.”

The certainty lives somewhere inaccessible, in tissue that can still be examined only after death.

That diagnostic gap has become harder to ignore. A new study in The BMJ, led by Daneshvar, estimated that at least 24.5 percent of former NFL players who died between 2016 and 2021 had chronic traumatic encephalopathy.

The researchers reached that estimate by taking the most conservative approach possible: they counted every player whose brain was not examined as though he did not have CTE. Even then, roughly one in four had the disease.

CTE is associated with years of repeated blows to the head. Over time, an abnormal form of the protein tau, which helps maintain the structure of brain cells, builds up in a distinctive pattern. The damage has been linked to problems with memory and thinking and, in more advanced disease, dementia.

But scientists still do not know why some people exposed to years of head impacts develop CTE while others apparently do not, or how often the disease occurs outside the groups whose brains have been studied most closely. Now, researchers are testing whether brain scans, blood tests, and other clues can help identify CTE during life. But each step forward has revealed new reasons the disease may be difficult to diagnose.

A Disease with Borrowed Symptoms

One of the biggest obstacles to diagnosing CTE during life is that its symptoms overlap with so many other conditions. Memory problems can resemble Alzheimer’s. Depression and anxiety have countless possible causes. Sleep disorders, medications, and other health problems can also shape the way a person thinks, feels, and behaves.

A history of football can tell a doctor something about risk, but not what is unfolding inside the brain. Researchers have also broadened their focus beyond concussions to include years of repeated head impacts, including hits that never cause obvious symptoms. A lineman may absorb them play after play without leaving the field or entering concussion protocol.

Some symptoms closely associated with CTE in the public imagination have proven surprisingly unreliable.

(What are the early warning signs of CTE? New clues emerge.)

“In the beginning, you heard a lot about personality changes—mood, anger, impulsivity,” says Michael Alosco, co-director of clinical research at Boston University’s CTE Center. “Those have been quite elusive. We don’t see strong associations with the tau of CTE.”

“Maybe people who are more aggressive are more likely to go into a high-impact sport,” he adds. “Maybe it’s head trauma. Our data haven’t shown that association.”

The danger runs in both directions. A doctor might miss CTE, or attribute symptoms to it while overlooking something treatable. Once a former athlete becomes convinced that he has the disease, a forgotten name or a bad day can take on concerning significance.

Building a Diagnosis

The likeliest path to diagnosing CTE may not be one decisive test, but several forms of evidence converging.

Blood tests could help by identifying diseases that look like CTE. In a 2026 JAMA Network Open study, Alosco and colleagues tested the Alzheimer’s blood marker p-tau217 in 231 people, including 177 former football players. It did not appear useful for detecting CTE, but it still appeared useful for detecting Alzheimer’s.  

The overlap can be deceptive. A former player with worsening memory may have CTE, Alzheimer’s, or some combination of the two. Tests that reveal one disease, or make another less likely, can help clarify a murky picture.

A separate 2026 brain-bank study highlighted how easily the diseases can blur together. Researchers excluded donors whose autopsies revealed Alzheimer’s disease or several other major neurodegenerative disorders. Still, among 99 people with advanced CTE who had developed dementia, 40 had been suspected of having Alzheimer’s during life.

(The disease no one wants to see.)

The finding does not mean that 40 percent of people with CTE are misdiagnosed with Alzheimer’s. It does, however, highlight how easily the diseases can masquerade as one another, even in people whose brains later showed advanced CTE and no evidence of Alzheimer’s.

The distinction matters. New drugs can slow Alzheimer’s disease in some patients, but no treatment can yet stop or reverse CTE.

A CTE Lock With an Alzheimer’s Key

The clearest path forward may be to see CTE’s defining pathology directly. Under a microscope, the disease leaves a distinctive signature: abnormal tau protein clustered around tiny blood vessels, often deep within the brain’s folds. Neil Vasdev, director of the Brain Health Imaging Centre at the Centre for Addiction and Mental Health and a professor of psychiatry at the University of Toronto, is trying to make those hidden deposits visible with PET imaging.

“The field has essentially been trying to open a CTE lock with an Alzheimer’s key,” Vasdev says. “Tau isn’t one thing. It folds into different shapes.”

Existing PET tracers can reveal Alzheimer’s tau, but CTE tau is folded differently.

“We don’t have the right-shaped key,” Vasdev says, “and it’s a target that likes to hide.”

In a 2024 Nature Communications study, Vasdev and his collaborators reported synthesizing and screening more than 150 molecules before identifying a promising tracer known as OXD-2314.

The search begins with donated brains. Vasdev’s team exposes tissue from people who died with confirmed neurodegenerative diseases, including CTE cases donated through Boston University’s brain bank, to experimental tracers. The goal is to find a molecule that binds tightly to CTE-related tau while ignoring the countless other proteins in the brain.

(A new blood test could speed up Alzheimer’s diagnoses. Will it lead to better treatments?)

A molecule that works on a slice of brain still has to prove itself in a living person. In a 2025 first-in-human study, four healthy volunteers received OXD-2314.  The tracer entered the brain without any reported adverse events. The trial was not designed to show whether the tracer could detect CTE. Instead, it showed the molecule could be used safely in people, clearing a path for studies of diseases marked by abnormal tau.

Vasdev says researchers have since begun scanning people as they investigate whether it can reveal CTE.

“The most exciting part is we are seeing a signal in living people right where we’d expect CTE,” he says.

But, a signal, he adds, is not a diagnosis.

“Right now, we’ve scanned some people,” Vasdev says. “It’s just the start of this validation road, and it’s too early to rely on.”

There is another complication. The molecular shape scientists associate with CTE may not belong exclusively to CTE.

“The more you dig into this, the grayer it becomes,” says Sami Barmada, a neurologist and director of the University of Michigan Brain Bank.

The tau may not tell the whole story. In a 2026 study, Barmada and colleagues found CTE-type tau filaments in the brains of two people who had Alzheimer’s disease along with LATE. This age-related condition can also affect memory.

The work suggests that tau’s shape alone might not be enough to identify CTE. Its location in the brain, and the absence of other diseases, may matter just as much.

That could mean a future scan needs to reveal not simply the presence of abnormal tau, but its geography. CTE leaves damage in a characteristic pattern. PET might show tau while MRI reveals where changes are occurring, and blood tests eliminate competing explanations, Barmada says.

“Just as important as the tests for something is the exclusion,” he says, “being able to check off the boxes of what is not.”

Waiting for the Answer

The final hurdle is proving that those clues really mean CTE.

The DIAGNOSE CTE Research Project is following former football players with clinical exams, biological samples, and brain imaging, with participants asked to consider eventual brain donation.

“We’re following people at different time points and asking for brain donation,” Alosco says. “Then we’ll know the truth at the end.”

A former player might give blood in his 60s, lie inside an MRI or PET scanner and return years later to do it again. Eventually, if he donates his brain, a neuropathologist can cut it into thin sections, stain the tissue and search beneath a microscope for the distinctive pattern of CTE.

Only then can researchers return to the blood samples and scans collected years earlier and ask which ones gave them the right answers.

“That’s why brain donation is the most precious gift someone can give,” Alosco says.

The process is slow, but it reveals something important: a biomarker that separates groups of former players in a research study is not necessarily good enough to diagnose the individual sitting across from a doctor. It has to reliably find CTE when the disease is there without repeatedly finding it when it is not.

For all the unanswered questions, researchers say the field is entering a new phase. In January 2027, the National Institute of Neurological Disorders and Stroke plans to convene a summit at the National Institutes of Health, bringing together scientists and other stakeholders to discuss how decades of research might finally be translated into clinical care.

For now, confidence remains patchy. Researchers say multiple lines of evidence point strongly toward CTE in some cases, while uncertainty persists in others. The challenge now is to determine what level of certainty is enough to help patients in the clinic.

“It's a really exciting time,” Alosco says. “We need to come together as a scientific community and see whether we can move what we've learned into practice.”