Repeated head impacts cause early neuron loss and inflammation in young athletes
NIH-funded study reveals brain changes long before chronic traumatic encephalopathy (CTE) develops
Research supported by the National Institutes of Health (NIH) shows that repeated head impacts from contact sports can cause early and lasting changes in the brains of young- to middle-aged athletes. The findings show that these changes may occur years before chronic traumatic encephalopathy (CTE) develops its hallmark disease features, which can now only be detected by examining brain tissue after death.
“This study underscores that many changes in the brain can occur after repetitive head impacts,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “These early brain changes might help diagnose and treat CTE earlier than is currently possible now.”
Scientists at the Boston University CTE Center, the U.S. Department of Veterans Affairs Boston Healthcare System and collaborating institutions analyzed postmortem brain tissue from athletes under age 51. Most of them had played American football. The team examined brain tissue from these athletes, using cutting-edge tools that track gene activity and images in individual cells. Many of these tools were pioneered by the NIH’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®. The researchers identified many additional changes in brains beyond the usual molecular signature known to scientists: buildup of a protein called tau in nerve cells next to small blood vessels deep in the brain’s folds.
For example, the researchers found a striking 56% loss of a specific type of neurons in that particular brain area, which takes hard hits during impacts and also where the tau protein accumulates. This loss was evident even in athletes who had no tau buildup. It also tracked with the number of years of exposure to repetitive head impacts. The findings thus suggest that neuronal damage can occur much earlier than is visible by the currently known CTE disease marker tau. The team also observed that the brain’s immune cells, called microglia, became increasingly activated in proportion to the number of years the athletes had played contact sports.
The study also revealed important molecular changes in the brain’s blood vessels. These changes included gene patterns that could signal immune activity, a possible reaction to lower oxygen levels in nearby brain tissue, and thickening and growth of small blood vessels. Together with these findings, the researchers identified a newly described communication pathway between microglia and blood vessel cells. The authors suggest that this crosstalk may help explain how early cellular problems set the stage for disease progression long before CTE becomes visible.
The study is one of the first to focus on younger athletes, shifting attention from advanced CTE in older people to the earliest cellular signatures of damage.
“What’s striking is the dramatic cellular changes, including significant, location-specific neuron loss in young athletes who had no detectable CTE,” said Richard Hodes, M.D., director of NIH’s National Institute on Aging (NIA). “Understanding these early events may help us protect young athletes today as well as reduce risks for dementia in the future.”
By revealing the earliest cellular warning signs, this work lays the foundation for new ways to detect brain effects of repetitive head injuries and potentially lead to interventions that could prevent devastating CTE neurodegeneration.
This research was supported by NINDS and NIA through grants F31NS132407, U19AG068753, RF1AG057902, R01AG062348, R01AG090553, U54NS115266, and P30AG072978.
Reference: Butler MLMD, Pervaiz N, Breen K. et al. Repeated head trauma causes neuron loss and inflammation in young athletes. Nature (2025). DOI: 10.1038/s41586-025-09534-6
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About the National Institute of Neurological Disorders and Stroke (NINDS): NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. https://www.ninds.nih.gov/
About the National Institute on Aging (NIA): NIA seeks to understand the nature of aging and diseases associated with growing older, with the goal of extending the healthy, active years of life. https://www.nia.nih.gov/
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit https://www.nih.gov/.
NIH…Turning Discovery Into Health®
Journal
Nature
Article Title
Repeated head trauma causes neuron loss and inflammation in young athletes
Article Publication Date
17-Sep-2025
BU study of young athletes finds neurodegeneration might begin before CTEa
These results have the potential to significantly change our perspective on contact sports.
Boston University School of Medicine
(BOSTON) This fall, tens of millions of people will be at risk for chronic traumatic encephalopathy (CTE), a degenerative brain disease caused by repeated head impacts from contact sports like football, soccer, and ice hockey, or military service. Researchers have long suspected that the brain begins changing years before CTE appears, but proof has been elusive because CTE can only be definitively diagnosed after death.
A new study led by researchers from Boston University Chobanian & Avedisian School of Medicine, published in Nature, has revealed a cascade of “repetitive head impact (RHI)-related brain injuries” resulting in brain cell loss, inflammation and vascular damage in young former contact sport athletes. Importantly, many of the changes were seen in athletes before the onset of CTE.
“These results have the potential to significantly change how we view contact sports. They suggest that exposure to RHI can kill brain cells and cause long-term brain damage, independent of CTE,” said corresponding author Jonathan Cherry, PhD, assistant professor of pathology & laboratory medicine and director of the digital pathology core at the BU CTE Center.
To identify the earliest changes from RHI, researchers performed single nucleus RNA sequencing on the frozen human brain tissue from 28 men between the ages of 25 and 51. They were divided into three groups: a control group of eight men who didn’t play contact sports; an RHI group comprised of eight American football players and a soccer player, none of whom were diagnosed with CTE; and a CTE group of 11 contact-sport athletes with low-stage (defined as Stage 1 or 2) CTE. All results were further validated and confirmed in larger sample sets and through comparison to other published studies.
As previously published, athletes diagnosed with low-stage CTE had significant inflammatory and vascular changes. However, this study showed similar levels of vascular injury and inflammation in athletes without CTE, suggesting that RHI-related brain injury is not solely dependent on CTE.
One of the most striking findings was a 56% loss of neurons, cells vital to normal brain function, in young athletes participating in contact sports. The loss of neurons was precisely at the cortical sulcal depths, the brain regions that undergo the highest mechanical forces during head impact injury, and where CTE first develops. Neuron loss was observed in all athletes, regardless of whether they had CTE.
“You don't expect to see neuron loss or inflammation in the brains of young athletes because they are generally free of disease. These findings suggest that repetitive head impacts cause brain injury much earlier than we previously thought,” said Cherry. “The risk for CTE is directly related to repetitive head impact exposure in contact sports. These results highlight that even athletes without CTE can have substantial brain injury. Understanding how these changes occur, and how to detect them during life, will help the development of better prevention strategies and treatments to protect young athletes.”
“This groundbreaking study shows that repetitive hits to the head, including concussions and the more frequent non-concussive impacts, cause brain damage in young people even before CTE. These findings should serve as a call to reduce head hits in contact sports at all levels, including youth, high school and college,” adds coauthor Ann McKee, MD, director of the BU CTE Center and William Fairfield Warren Distinguished Professor of Neurology and Pathology at BU.
About the BU CTE Center
The BU CTE Center is an independent academic research center at the Boston University Avedisian & Chobanian School of Medicine. It conducts pathological, clinical and molecular research on CTE and other long-term consequences of repetitive brain trauma in athletes and military personnel. For people considering brain donation, click here. To support its research, click here.
This work was supported by grant funding from: NINDS (F31NS132407), NIH (U19-AG068753), NIA (AG057902, AG062348, AG090553), NINDS (U54NS115266), National Institute of Aging Boston University AD Center (P30AG072978); Department of Veterans Affairs Biorepository (BX002466), and the Department of Veterans Affairs Career Development Award (BX004349), BLRD Merit Award (I01BX005933).
Journal
Nature
Method of Research
Experimental study
Subject of Research
Cells
Article Title
Repeated head trauma causes neuron loss and inflammation in young athletes
Article Publication Date
17-Sep-2025
Soccer headers and brain health: Study finds changes within folds of the brain
MINNEAPOLIS — In amateur soccer players, more frequent heading, or using the head to control or pass the ball, is linked to alterations within the folds of the brain, according to a study published on September 17, 2025, in Neurology®, the medical journal of the American Academy of Neurology. The study does not prove that soccer heading causes brain changes, it only shows an association.
“While taking part in sports has many benefits, including possibly reducing the risk of cognitive decline, repetitive head impacts from contact sports like soccer may offset those potential benefits,” said study author Michael L. Lipton, MD, PhD, of Columbia University in New York City. “Our study found that people who experienced more impacts from headers had more disruptions within a specific layer in the folds of the brain, and that these disruptions were also linked to poorer performance on thinking and memory tests.”
The study included 352 amateur soccer players with an average age of 26 and 77 athletes in non-collision sports with an average age of 23.
Athletes’ soccer activity was surveyed to estimate the number of head impacts over one year. Soccer players were divided into four groups with the highest group having an average of 3,152 headers per year compared to 105 headers in the lowest group.
Athletes had brain scans. Researchers used the scans to examine the microstructure of the juxtacortical white matter within the folds of the brain. This layer of white matter lays alongside the gray matter of the cerebral cortex, the outer layer of the brain.
When analyzing scans, researchers looked at how water molecules moved in the folds of this brain layer.
They found that soccer players in the highest group had much greater disruption in the microstructure of this area of the brain compared to soccer players in the lowest group and non-collision sport athletes. As the number of headers increased, the organization of water molecule movement deteriorated, indicating more disruptions and suggesting worsening of the brain’s microstructure.
Athletes took tests to examine thinking and memory skills. Researchers found that players with worse performance on tests had more disorganized movement of water molecules in this area of the brain.
Researchers found that disruptions in the folds of the orbitofrontal brain region, just above the eye sockets, partially affected the relationship between repeated head impacts and thinking and memory performance.
“Our findings suggest that this layer of white matter in the folds of the brain is vulnerable to repeated trauma from heading and may be an important place to detect brain injury,” said Lipton. “More research is needed to further explore this relationship and develop approaches that could lead to early detection of sports-related head trauma.”
A limitation of the study was that the number of headers over the previous year was estimated based on athlete responses and may be influenced by their ability to remember this information accurately.
The study was supported by the Dana Foundation David Mahoney Neuroimaging Program and the National Institute of Neurological Disorders and Stroke.
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Journal
Neurology
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