No, chronic traumatic encephalopathy (CTE) is not caused only by head trauma. Repeated head impacts are the primary risk factor and likely required, but new research shows additional biological processes, including immune activation and DNA damage, help drive the disease long after injuries occur. These findings explain why only some people with similar exposure to head impacts develop CTE.
What is CTE?
CTE is a progressive neurodegenerative disease linked to repeated head impacts, most often diagnosed after death by the presence of abnormal tau protein in specific brain regions. Symptoms can include problems with thinking, mood, and behavior that may progress to dementia.
CTE is definitively diagnosed postmortem by its characteristic tau pattern, and it is associated with repeated head impacts, not a single isolated concussion.
For background, see the National Institute of Neurological Disorders and Stroke overview of CTE and diagnostics, which reflects current consensus criteria (NINDS), and the Boston University CTE Center explainer on tau pathology and risk from repeated head impacts (BU CTE Center).
How does CTE develop after head trauma?
Head impacts start the process, but they are not the whole story. Mechanical forces can injure neurons and supporting cells, disrupt the blood brain barrier, and trigger brain immune responses. Over time, this biology can lead to abnormal tau accumulation, inflammation, and neuronal dysfunction.
Multiple studies suggest microglia, the brain’s immune cells, become persistently activated after repeated head impacts. This chronic immune activity may contribute to ongoing tissue injury and the spread of toxic tau, similar to mechanisms observed in Alzheimer’s disease. The end result is a gradual neurodegenerative cascade that can unfold years after athletic play or military service has ended.
What did the new study actually find?
A team led by Harvard Medical School, Boston Children’s Hospital, Mass General Brigham, and Boston University analyzed postmortem human brain tissue with single cell genomic methods to look for somatic, or acquired, DNA changes in neurons (Harvard Medical School summary). Key findings:
- Distinct DNA damage patterns in CTE. Neurons from people with CTE showed abnormal patterns of somatic genome damage that closely resembled patterns seen in Alzheimer’s disease.
- Changes absent in repeated head impact without CTE. Individuals who had repeated head impacts but did not have CTE at autopsy did not show these DNA changes.
- Signal of accelerated biological aging. The extent of genome damage in CTE resembled more than a century of excess aging in the affected brain samples, indicating long running processes beyond the initial trauma.
Based on these results, the authors propose that immune activation years after trauma contributes to CTE pathogenesis, aligning CTE with Alzheimer’s at a mechanistic level and highlighting potential shared therapeutic targets.
This study does not show that CTE occurs without head injury. It suggests that, after head impacts, downstream immune and DNA damage processes help determine who develops CTE.
Does this mean CTE can occur without head injury?
No. The strongest and most consistent risk factor for CTE is repeated head impacts, especially from contact sports and blast or impact exposures in military settings. The new data add that immune and genomic damage pathways are important in disease development, which helps explain variable risk across individuals with similar exposure.
Public health guidance continues to focus on limiting exposure to repeated head impacts and improving recognition and management of concussive and sub-concussive events. See consensus guidance and background from NINDS and the BU CTE Center (NINDS, BU CTE Center).
Why does this matter for prevention and treatment?
Understanding that CTE involves more than the initial trauma opens two avenues:
- Prevention. Reduce repeated head impact exposure through rule changes in sports, improved techniques, and better equipment standards. These measures address the initiating risk factor.
- Therapeutic targets. If chronic immune activation and DNA damage pathways drive progression, drugs that modulate microglial inflammation or protect neuronal genomes could slow or prevent disease, similar to strategies pursued in Alzheimer’s research. The overlap suggests opportunities for shared biomarkers and treatments, though these require rigorous testing.
The study also underscores the need for biomarkers that detect disease processes in living people, so clinicians can identify at risk individuals early and evaluate potential therapies before extensive degeneration occurs.
What are the limitations and what comes next?
The new findings are important, but they come with caveats:
- Postmortem and observational. The study examined brain tissue after death, so it cannot establish causation or track changes over time.
- Selected samples. Brain bank donors are not representative of everyone with head impact exposure, which can introduce selection bias.
- Small cohorts and single regions. Analyses covered specific brain areas and a limited number of cases. Larger, multi region studies are needed.
Next steps include validating these DNA damage signatures in independent cohorts, mapping when they appear relative to head impact history and symptoms, and testing whether immune modulating or neuroprotective therapies can alter these pathways.
Bottom line, repeated head impacts put people at risk for CTE, and emerging evidence shows that long lasting immune and genomic damage processes help drive who develops the disease and how it progresses. That dual picture, trigger and downstream biology, is shaping how scientists think about prevention, diagnosis, and future treatments.