Hidden genetic damage is part of CTE, too, study finds

Research from Dr. Ann McKee of Boston University and other scientists examined the brains of people with and without CTE. (Steven Senne/AP via CNN Newsource)

The neurologic disease called chronic traumatic encephalopathy or CTE has most often been found in people who experienced repeated blows to the head while playing contact sports and there’s now evidence of genetic damage inside the brain, too.

The researchers examined the brains of football players and others with the rare neurological disease, and the genetic damage they found looks similar to what they see in the brains of people with Alzheimer’s disease. The damage was so extensive that it was the equivalent of hundreds of years of aging.

CTE typically develops years after someone has received repeated blows to the head. Symptoms can include memory loss, impulse control problems, anxiety, depression and anger issues. It’s most often seen in people who play sports like football, hockey and soccer, but it’s also been detected in the brains of soldiers who have been injured in explosions and in some people who experienced domestic violence.

The disease was first identified nearly 100 years ago in boxers – at the time, scientists called it “punch-drunk syndrome” – but there’s still much that experts don’t know about CTE. Not everyone with repeated head trauma develops the condition, and scientists don’t totally understand why or even how head trauma can lead to this disease.

Dr. Chris Walsh, co-author of the study published Thursday in the journal Science, says there are still people who deny that CTE is even a disease. The latest research, he said, should change naysayers’ minds.

“We feel like this study helps establish that CTE is something distinct from just repetitive head trauma. It represents a more gradually developing pathological process and is a well-defined entity,” said Walsh, who is chief of the Division of Genetics and Genomics at Boston Children’s Hospital and an investigator at the Howard Hughes Medical Institute.” We suspect it involves immune activation in a way similar to Alzheimer’s disease.”

At this point, scientists don’t have a simple blood test or scan that can detect CTE in a living person. The only way to make a definitive diagnosis is to take thin slices of the brain after the person’s death and use a microscope to look for an abnormal accumulation of tau, a protein that stabilizes certain elements of the brain. Too much tau can damage blood vessels and brain cells, and this buildup is also a hallmark of Alzheimer’s.

The brain is made up of a mosaic of cells that each have their own genome. Every time a stem cell divides, it accumulates mutations. The new study used sequencing and amplification technology only recently made available to look at the genes of single cells in hundreds of neurons in the prefrontal cortex, the part of the brain used for decision-making and other thinking skills.

The researchers compared the results from four groups: 15 people who had repeated hits to the brain and were diagnosed with CTE; four people who had repeated head injuries but hadn’t developed CTE; 19 people without a history of head injuries or signs of CTE; and seven people who had Alzheimer’s.

Among the people with CTE, the cells showed genomic damage that looked similar to the brains of people who had Alzheimer’s. The people who had repeated brain trauma but were not diagnosed with CTE did not have the same kind of damage.

“Cells carry a bar code of their whole developmental history, including reflecting environmental influences, and that’s what’s happening in CTE,” Walsh explained. “The abnormal environment created by the repeated trauma damages the genomes of the cells.”

With better understanding of the mechanisms that cause CTE, Walsh hopes the work can eventually lead to developing treatments. Because brain damage with CTE looks similar to Alzheimers, it may even be possible to use therapies for CTE patients that helped people with Alzheimer’s, but much more research will be needed before that could happen.

The new study builds on recent research indicating that brain damage from repeated blows to the head can show up much earlier than the excessive tau markers that are seen with CTE become clear.

A 2023 study showed that the brain’s immune cells were increasingly activated in proportion to the number of years an athlete played contact sports, suggesting that early cellular damage may be setting the stage for the disease to progress.

A 2020 study also found that the risk of CTE doubles for every 2.6 years spent playing football. The condition has been reported in people as young as 17, meaning by the time a football player goes pro, they have experienced hundreds of thousands of hits to the head, and that damage seems to be adding up.

The NFL has implemented several rule and equipment changes to reduce the number of head injuries, and the number of concussions has declined, with data from the 2024 season showing the lowest number of concussions since tracking began in 2015. Other sports leagues including the NHL, MLS and the English Premier League have also made changes to reduce the number of concussions among their playeres.

But experts say it’s not just concussions that are the problem; any hit to the head can cause damage. Some suggest that if children really want to play football, their parents might skip early leagues, which can start as early as age 5, and instead wait until children turn 14 or 18 to let them play tackle football. The American Youth Soccer Organization doesn’t recommend heading the ball before the age of 10, and coaches are not encouraged to teach or practice heading at early ages.