Boston University CTE study: Genes may play major role in CTE severity

A new study out of the Boston University CTE Center reveals that a person’s genes could play a key role in determining the severity of the chronic brain disease.

Chronic traumatic encephalopathy is a progressive degenerative disease of the brain found in people, often athletes, with a history of repetitive brain trauma. However, the occurrence and severity of CTE varies widely among those with similar repetitive head impacts.

Now, BU researchers have found that a genetic variant carrying the technical label APOE e4 may increase risk for CTE severity among older individuals with repetitive head impacts.

The CTE scientists determined that having this genetic variant makes a person more than twice as likely to develop a more severe form of CTE.

“This study provides the most concrete evidence to date that APOE e4 is a risk factor for CTE-related pathological and clinical outcomes,” said corresponding author Jesse Mez, director of the BU Alzheimer’s Disease Research Center Clinical Core and a BU CTE Center investigator.

The researchers studied the brains of dead individuals exposed to repetitive head impacts through contact sports or military service — 294 who developed CTE and 70 who did not.

The scientists then analyzed their neurological findings based on their APOE status and found that APOE e4 carriers were 2.34 times more likely to have more severe CTE than those without.

More severe CTE was determined by both CTE stage (I through IV) and a quantitative analysis of abnormal tau protein burden, which scientists look at to find the underlying disease.

“Our research team has shown that among football players, an individual’s odds of developing a more severe stage of CTE double every additional 4.4 years of play,” Mez said. “Specifically, for football players over age 65, having APOE e4 had an effect on CTE severity equivalent to playing an additional seven years of football, meaning it more than doubled risk.”

According to the researchers, these findings provide insight into how CTE progresses, which may provide new targets for developing treatments to slow or stop CTE progression.

“Understanding genetic underpinnings of CTE pathology may provide insights into disease mechanism and offers a precision medicine approach to harm reduction, including guiding decisions regarding contact sport play and providing a target for therapies,” Mez added.

APOE e4 can be readily identified in people through a common blood test that can be ordered by a doctor, and it’s provided by 23andMe. Researchers commonly test for it in studies of living individuals.

Mez said, “There is an ongoing discussion as to the implications of testing because it only alters risk, but does not provide a definite answer as to whether a disease will occur and understanding/interpreting risk is hard.”