Brain injuries from contact sports share genetic traits with Alzheimer’s

A new study shows that brains with chronic traumatic encephalopathy (CTE) carry DNA damage patterns that align with what scientists see in Alzheimer’s disease.

The team examined neurons from people diagnosed after death and found genetic damage linked to disease processes, not just the battering of repeated head hits.

How CTE changes neurons

The researchers mapped DNA in single brain cells from the prefrontal cortex and saw extra mutations in neurons from people with CTE.

The experts also found distinct patterns of short deletions that point to specific sources of cellular stress.

By reading DNA at the level of a single cell, the experts were able to distinguish genuine double-stranded mutations from single-stranded damage. They found that both forms were present in neurons affected by CTE.

Similar mutational signatures

The work was led by Dr. Chris A. Walsh at Boston Children’s Hospital (BCH). His research focuses on somatic changes in the brain and how they shape neurodevelopment and neurodegeneration.

The analysis also compared CTE brains to those from people with Alzheimer’s and to neurotypical controls.

The CTE and Alzheimer’s samples showed similar mutational signatures, while controls showed much lower burdens.

CTE beyond head injury

People who had repeated head impacts but did not meet criteria for CTE did not show these mutation patterns. This finding pushes the field toward causes that unfold long after the last game or deployment.

Recent research found neuron loss and immune changes in young people with years of exposure to hits, even before the classic tau clumps that define CTE appear.

The data suggest a slow biological cascade that starts early and may accelerate in some individuals.

“Our results suggest that CTE develops through some process in addition to head trauma. We suspect it involves immune activation in a way similar to Alzheimer’s disease, happening years after trauma,” said Dr. Walsh.

Alzheimer’s damage and CTE neurons

The team reported more double-stranded single nucleotide changes in CTE neurons that matched a pattern linked in earlier work to oxidative stress. Oxidative injuries arise when reactive molecules nick DNA faster than cells can patch it.

The experts also observed an excess of short DNA deletions that resemble COSMIC signature ID4, a cataloged pattern of short DNA deletions.

This pattern has been connected in other contexts to topoisomerase activity and transcription related stress.

CTE patterns seen in Alzheimer’s

Prior evidence shows that neurons accumulate somatic mutations with age and that neurodegenerative conditions carry higher burdens.

The new results place CTE inside that broader picture and tie its patterns to those seen in Alzheimer’s.

One proposed contributor is topoisomerase 1, an enzyme that relieves DNA twisting stress. When transcription runs hot, or repair systems fall behind, cuts and misrepairs can stack up in vulnerable neurons.

Head trauma versus disease

Investigators analyzed hundreds of single neurons taken from 15 individuals with CTE and compared them with neurons from people with repetitive head impacts without CTE, neurotypical controls, and people with Alzheimer’s.

The balanced study design enabled the researchers to distinguish the effects of trauma exposure from the underlying biology of the disease itself.

They used two sequencing modes to distinguish true mutations from transient DNA lesions. That distinction matters because single-stranded lesions can mark ongoing stress, while double-stranded mutations record permanent changes.

Processes beyond physical force

Somatic mutations in protein coding genes clustered in pathways essential for neuron function.

That enrichment hints at how small, private DNA changes across many cells might add up to network level failure over time.

The burden in people with repeated head impacts but no CTE matched the controls. This indicates that the disease-specific signatures arise from processes beyond physical force alone, likely involving immune and vascular factors.

Treatments for Alzheimer’s and CTE

If CTE shares core mutational processes with Alzheimer’s, overlapping treatments might help both conditions.

Therapies that dial down oxidative damage or stabilize transcription related stress could, in theory, slow decline.

This work also supports efforts to reduce total exposure to head impacts in youth and amateur sports. A smaller dose of hits should mean a smaller chance of triggering long running injury programs in the brain.

Potential for early detection

Early detection may be possible if blood or cerebrospinal fluid can capture fragments that reflect the same mutational processes.

A laboratory signal that rises years before symptoms would change the game for prevention.

Policy will still hinge on simple rules that cut exposures, like fewer contact practices and smarter scheduling. The biology adds urgency to those choices and offers paths for medical interventions when rules are not enough.

Future research directions

The study used postmortem samples, so it cannot prove when each mutational process started. Prospective work in living volunteers, paired with fluid markers and imaging, will be needed to time the cascade.

The analysis focused on the prefrontal cortex, a region tied to cognition and impulse control. Other regions, such as the hippocampus and deep white matter, could show different vulnerability maps.

Microvascular strain has long been implicated in CTE pathology around small vessels. One earlier paper highlighted vessel related injury alongside early tau changes, a pairing that fits with the immune and DNA damage patterns reported here.

The field is moving toward tests that integrate immune markers, vascular health, and neuronal DNA repair capacity. Those measures could sort who is at highest risk and who stands to benefit most from preventive care.

The study is published in the journal Science.

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