Researchers are making significant progress toward developing diagnostic tools to identify chronic traumatic encephalopathy (C.T.E.) in living patients, a breakthrough that could transform how the disease is understood and managed. C.T.E., a degenerative brain condition linked to repeated head trauma, has so far only been diagnosed through post-mortem examinations, a limitation that has hampered efforts to treat its symptoms such as memory loss, mood swings, and behavioral changes.
Recent findings underscore the urgency of establishing a reliable diagnosis during life. A study released last month estimated that at least 25% of former National Football League (NFL) players who died between 2016 and 2021 may have had C.T.E., with some experts suggesting the prevalence could be significantly higher. Without antemortem diagnostic capabilities, physicians rely on excluding other neurodegenerative diseases, rendering C.T.E. diagnoses in living individuals “nondefinitive.”
Scientists are focusing on advanced imaging techniques and blood tests to overcome this challenge. Positron emission tomography (PET) scans, already utilized for Alzheimer’s disease and other brain conditions, are at the forefront of these efforts. The key difficulty lies in detecting abnormal tau proteins, which accumulate in unique shapes around neurons and blood vessels due to repeated brain trauma. These clusters ultimately lead to brain cell death and shrinkage.
Researchers such as Neil Vasdev, director of the Brain Health Imaging Centre in Toronto, have developed novel radiochemistry tracers designed specifically to bind to the tau protein formations unique to C.T.E., thus enabling their visualization on PET scans. These tracers differ from those targeting Alzheimer’s tau, which previously limited diagnostic accuracy. Vasdev’s team recently reported the safe use of a new tracer, 0XD-2314, in living volunteers and is now testing its effectiveness in patients with suspected tau accumulation.
Parallel efforts at the University of California, Los Angeles (UCLA), led by neurosurgeon Julian Bailes, involve developing biomarkers that highlight C.T.E.-related tau on PET scans. A Phase 3 clinical trial is currently assessing these imaging tools’ diagnostic accuracy.
Given the expense and complexity of PET scans, researchers are also investigating blood-based biomarkers reflecting neuron damage and inflammation associated with C.T.E. Boston University’s CTE Research Center, under the leadership of Michael Alosco, has assembled a large cohort donating blood samples during life and brain tissue posthumously. This repository enables scientists to correlate blood markers with definitive neuropathological diagnoses.
Although no treatments currently exist to halt or reverse C.T.E., obtaining a diagnosis during life may provide significant benefits. Families report that understanding the illness behind diverse behavioral and cognitive symptoms helps them manage care and make longer-term plans. Eleanor Perfetto, whose late husband, former NFL player Ralph Wenzel, was diagnosed with C.T.E. after death, noted that a timely diagnosis might have helped her better understand his early memory lapses and erratic behavior.
Experts emphasize that while C.T.E. is most prevalent among professional athletes in high-impact sports such as football, boxing, and rugby, it also affects military personnel exposed to repeated blasts and survivors of domestic abuse. More data is needed to determine its prevalence at amateur and youth levels.
Research into diagnostic techniques is funded largely by the National Institutes of Health and conducted through collaborations among institutions including Boston University and the Cleveland Clinic. The UNITE Brain Bank at Boston University houses a growing collection of over 1,800 donated brains, nearly half of which have been confirmed to have C.T.E., providing an invaluable resource for ongoing studies.
Scientists cautiously optimistic about these developments view a reliable diagnostic test for C.T.E. as inevitable, though complex. “It’s hard, unglamorous work,” Vasdev said, highlighting the dedication required to translate decades of advances in chemistry and neuroimaging into a practical clinical tool that could one day improve outcomes for those affected by this devastating disease.