Gene variant increases brain inflammation in those with repetitive head impacts

FOR IMMEDIATE RELEASE, November 20, 2025

Contact: Gina DiGravio, 617-358-7838, ginad@bu.edu

Gene Variant Increases Brain Inflammation in Those with Repetitive Head Impacts

Findings underscore the importance of TMEM106B as a potential therapeutic target in CTE and related diseases

Boston—Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI). However, individuals with similar RHI exposure have shown differing pathology, suggesting a role for genetic variation. While a common Transmembrane Protein106B (TMEM106B) risk variant has been associated with greater CTE severity, its mechanism has remained unclear until now.

TMEM106B helps regulate lysosomes—tiny recycling centers inside cells—and is especially important for microglia, the brain’s immune cells. Changes in this gene can alter how microglia clear waste and respond to damage, affecting inflammation throughout the brain.

A new study from BU’s CTE Center has found that a genetic difference in the TMEM106B gene can make brain inflammation worse in people who have repeated head injuries, making them more likely to develop serious brain problems like CTE and dementia. This is the first time anyone has shown that this gene variant changes how the brain’s immune cells (called microglia) react in CTE, connecting a genetic factor directly to the way the brain responds to repeated head injuries. This finding could lead to its use as a genetic marker predicting who may be most vulnerable.

“These findings explain why some athletes and others with repeated head injuries are at higher risk for brain diseases. Knowing this gene increases risk means we may someday be able to identify people who should be extra careful to protect their brains or could benefit from new treatments,” says corresponding author Thor Stein, MD, PhD, associate professor of pathology & laboratory medicine at Boston University Chobanian & Avedisian School of Medicine and VA Boston Healthcare System.

Retrospective clinical data including contact sports history, levels (high school, college, etc.) played and years played at each level, was collected through online surveys, telephone interviews with next-of-kin and by reviewing clinical records. Additionally, the researchers examined brains from the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank of people who had a history of repeated head injuries. They analyzed their DNA to see if they had a certain type of TMEM106B gene. They then compared signs of brain inflammation, damage and memory problems between people with and without the gene variant.

In people older than 65, having the TMEM106B risk gene more than doubled the chances of developing worse CTE, similar to the effect of playing over eight years of contact sports. For those 65 or younger, carrying the TMEM106B gene variant was linked to a much higher risk of dementia.

“These results pave the way for more personalized approaches to preventing and treating brain diseases caused by repeated head injuries,” adds Stein. “Our hope is that understanding the role of TMEM106B will open up new possibilities to improve brain health and protect those most at risk.”
 

These findings appear online in the journal Acta Neuropathologica.

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 study was supported by National Institute of Aging Boston University AD Research Center, P30AG072978-McKee, P30AG072978-McKee, P30AG072978-McKee, P30AG072978-McKee, P30AG072978-McKee, P30AG072978-McKee, P30AG072978-McKee,P30AG072978-McKee, P30AG072978-McKee, P30AG072978-McKee, P30AG072978-McKee, National Institute of Aging Boston University AD Research, P30AG072978-McKee, National Institute of Aging, R01AG090553, R01NS132290, R01AG087199,R01NS139383, P30AG066514-06, R01NS139383, R01AG075876-Zhang, Stein, Zaia, National Institute of Neurological Disorders and Stroke, R01NS142076, R01 NS119651, R01NS093870, RF1NS122854- Alosco, U54NS115266-McKee, U54NS115266, U54NS115266-McKee, Veterans Affairs, BX004349, National Center for PTSD, U.S. Department of Veterans Affairs, NIH/NIA, 3P30-AG13846-23,EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT, 5R01HD104772, National Institute of Nursing Research, 5R01 NR020752-03, NIA, R01AG061028, National institute of Aging, 1RF1NS122854, National Institute of Aging, National Institute of Neurological Disorders and Stroke, 5R01 NS119651-04, National Institutes of Health, 75N92024R0245,National Institute of Neurological disorders and Stroke, 1U01 NS137483-01, Concussion Legacy Foundation, Andlinger Foundation, WWE, United States Department of Veterans Affairs, Veterans Health Administration, Veterans Affairs Biorepository, BX002466, BLRD Merit Award,I01BX005933 (CTE-AD), Alzheimer’s Association, NIRG-305779, NIRG-362697, National Institute of Neurological Disorders and Stroke, RF1NS122854- Alosco, National Heart, Lung and Blood Institute, 75N92019D00031, Department of Defense Peer Reviewed Alzheimer’s Research Program, PRARP #13267017, and Military Exposures Research Program Award United States (U.S.) Department of Veterans Affairs Biomedical Laboratory R& D Service (ALS MERP), 1I01BX005161.

Note to Editors:

Michael L Alosco receives research support from Life Molecular Imaging Inc. He also receives Royalities from Oxford University Press Inc and receive honorarium from Michael J Fox Foundation for services unrelated to this study. Yorghos Tripodis reports payment to self by the American Medical Association for editorial services. Douglas Katz receives Royalties from Demos/Springer publishers for Textbook on TBI with chapter on CTE Daniel H. Daneshvar conducts Expert medico-legal work related to TBI and SCI, receives research and clinical support from the NFLPA, and is a Member of NFLPA Mackey-White Health and Safety Committee.