Scientists have discovered how a gene strongly linked to Alzheimer’s disease may also trigger seizures by disrupting the brain’s energy supply.
The findings, from researchers at the University of Illinois Urbana-Champaign, suggest that an existing blood pressure medication could potentially reduce this dangerous brain hyperactivity.
The gene, called APOE4, is known to significantly increase the risk of developing Alzheimer’s disease compared with the more common APOE3 version.
Researchers have also observed that people with Alzheimer’s frequently experience seizures or abnormal brain activity, which can worsen memory loss and speed up disease progression. However, it has not been clear why this happens.
To investigate, scientists studied mice carrying the human APOE4 gene. They found that seizure activity began surprisingly early, during a stage roughly equivalent to a human in their 30s.
Younger mice showed no signs of the problem, suggesting that harmful brain changes may start long before symptoms appear.
The team also examined how another Alzheimer’s feature—tau protein tangles—affected seizures.
Female mice with both APOE4 and tau tangles experienced more severe seizures than males, reflecting a similar pattern seen in humans, where women are more likely to develop Alzheimer’s disease. Researchers say this difference may help explain why some people are more vulnerable than others.
Looking deeper, the scientists discovered that APOE4 reduces levels of a key protein that helps nerve cells control their activity. This protein acts like a pump that moves sodium and potassium in and out of cells, allowing neurons to function normally. When the pump’s activity drops, brain cells become overly excitable, which can lead to seizures.
The pump relies on ATP, the molecule that provides energy to cells. In APOE4 mice, ATP levels were lower, along with the enzymes that produce it. Without enough energy, the pump cannot keep neurons stable, leading to abnormal brain activity.
To see if restoring energy could help, the researchers treated the mice with terazosin, a drug already used to treat high blood pressure. Previous studies had suggested that the drug can boost the production of ATP-making enzymes. After treatment, ATP levels in the brain increased, and seizure activity decreased significantly.
The researchers then tested a combination approach that further improved energy production in brain cells. This strategy produced even stronger effects, reinforcing the idea that boosting cellular energy could help control seizures in people with the APOE4 gene.
Scientists believe these findings could open the door to new treatments for Alzheimer’s-related brain hyperactivity. Because terazosin is already approved for medical use, it may be possible to test it more quickly in human studies. The team also plans to explore whether increasing energy levels in the brain could slow memory decline or disease progression.
The study highlights the importance of the brain’s energy system in maintaining normal function. It also suggests that lifestyle factors that support energy production, such as exercise, might play a protective role.
While more research is needed, the discovery offers hope that targeting the brain’s energy pathways could reduce seizures and possibly improve outcomes for people at high risk of Alzheimer’s disease.
