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Chronic traumatic encephalopathy (CTE) is an irreversible degenerative brain disorder typically diagnosed posthumously. The clinical symptoms, which include memory loss, impaired decision-making, attention deficits, and behavioral changes, have been notably observed in former athletes and military personnel. Unfortunately, definitive diagnosis can only be made after death, relying on the detection of tau protein deposits around blood vessels in the brain.
Recent advancements in the understanding of CTE, highlighted in a study released Wednesday, may pave the way for identifying preclinical biomarkers of the disease. This is crucial for implementing preventative measures as awareness around the dangers of concussions and head injuries has significantly increased, especially following diagnoses in high-profile athletes.
CTE is particularly prevalent among sports players engaged in contact sports, notably football, and predominantly affects young male athletes. While the overall prevalence of CTE in the wider population remains largely unknown, a 2023 study documented in JAMA Neurology revealed that over 40% of athletes who died before the age of 30, after participating in contact sports, exhibited signs of early-stage CTE.
The recent research conducted by the Boston University Chobanian & Avedisian School of Medicine and published in the journal Nature demonstrates that cellular damage can occur long before the usual tau protein deposits that are characteristic of CTE.
The study involved an analysis of 28 brain tissue samples from individuals aged 51 or younger at the time of death, categorized into three groups: a control group with no exposure to repetitive head impacts (RHI), a second group exposed to RHI but not showing CTE markers, and a third group with early-stage CTE.
Utilizing single-cell RNA sequencing—which allows for detailed gene activity profiling in individual cells—the investigators found that subjects who had experienced repeated impacts but did not yet show CTE pathology had already begun to exhibit inflammatory responses, vascular impairment, and cellular damage commonly associated with CTE, even in the absence of tau proteins. Specifically, the RHI-exposed individuals displayed an average of 56% neuronal loss in certain areas of the brain when compared to the control group, implying significant brain damage akin to that observed in early-stage CTE.
“The findings indicate that brain damage caused by RHI occurs even when CTE markers are absent,” explained Jonathan Cherry, an assistant professor of pathology and laboratory medicine at Boston University and the corresponding author of the study. He emphasized that not every athlete with exposure to repetitive head injuries will develop CTE, but the study underscores that the associated neurological damage remains significant.
Commenting on the findings, Kevin Bieniek, a professor of pathology and laboratory medicine at the University of Texas at San Antonio who did not take part in the study, described it as “elegant” and “unbiased.” He remarked that the study pushes the understanding of disease pathophysiology beyond the conventional tau protein parameters and noted the benefits of focusing on younger individuals to eliminate age-related brain pathology confounding factors.
Although the scope of this study is small, the researchers believe their findings could lead to the identification of new biomarkers for diagnosing RHI-related brain damage. Bieniek suggests that these insights could open avenues for two types of therapeutic interventions: one aimed at mitigating neuronal loss and another designed to modulate the inflammatory responses that arise after RHI.
In strategizing risk management in contact sports, this study reinforces that avoiding overtly severe injuries is not the sole priority. Many of the athletes in both the CTE and RHI groups had not sustained diagnosed concussions (meaning they did not report symptoms following impacts), yet they still exhibited damage as a result of repeated minor injuries.
“There are athletes diagnosed with CTE who have never had a formally recognized concussion,” added Cherry. “These non-concussive, sub-concussive blows to the head are believed to be the principal drivers of this damage.”
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