Protein imbalances that increase brain cell excitability may explain why individuals with Alzheimer’s disease (AD) who also experience seizures demonstrate more rapid cognitive decline than those who do not experience seizures. These imbalances may be present in the brains of individuals before the onset of AD symptoms, according to new research from a team at the Perelman School of Medicine and published in Brain.
The team finds that an existing drug called rapamycin, initially developed as an immunosuppressant for organ transplant patients that suppresses signaling between neurons, was able to regulate the overexcited neurons in animal models of AD and seizures, and preserve cognitive function, like memory and the ability to learn new things.
Previous research has shown similar brain activity in individuals with AD who experience epilepsy. Additionally, many individuals with AD have also experienced at least one seizure, and previous research has shown that these seizures cause a more rapid progression of the disease, and worsen cognitive impairment, like trouble with memory or learning. However, researchers have not been able to identify the underlying connections between AD and seizures.
“Experts used to believe that seizures were an unfortunate byproduct of the neurodegeneration that causes Alzheimer’s disease, but now we see that seizures are actually advancing the disease itself,” says the study’s co-senior author, Frances E. Jensen, chair of Penn’s Department of Neurology. “Now that we have identified the mechanisms that cause neurons to get over-excited and lead to seizures that accelerate AD, we can explore therapies, like rapamycin, that can reverse the imbalance, and slow AD progression.”
“By the time many individuals are diagnosed with Alzheimer’s disease and start receiving treatments, their disease is advanced, and they have lost significant cognitive function,” says Aaron Barbour, a postdoctoral researcher in the Department of Neurology, and co-senior author. “Our research is an exciting step towards being able to intervene with a treatment before symptoms develop to slow the devastating effects of the disease.”
Read more at Penn Medicine News.
