For decades, researchers have recognized that Alzheimer’s disease is marked by the buildup of toxic protein fragments in the brain. What has remained unclear is exactly how and where those harmful fragments are generated.

In a new study, scientists at Northwestern University report that they have identified both the location and timing of this toxic buildup in Alzheimer’s patients. The team also found that an inexpensive drug already approved by the Food and Drug Administration (FDA) can interrupt the process before the damage begins.

Using a combination of animal models, lab-grown human neurons, and brain tissue from individuals at high risk for Alzheimer’s, the researchers focused on a particularly harmful fragment known as amyloid-beta 42. They discovered that this peptide accumulates inside synaptic vesicles, the small sacs neurons use to release chemical signals and communicate with one another.

When the scientists treated animals and human neurons with levetiracetam, a widely prescribed anti-seizure medication that has been available for decades, the drug blocked the formation of amyloid-beta 42. By preventing production of the peptide, levetiracetam stopped the chain of events that leads to amyloid plaque buildup.

“While many of the Alzheimer’s drugs currently on the market, such as lecanemab and donanemab, are approved to clear existing amyloid plaques, we’ve identified this mechanism that prevents the production of the amyloid-beta 42 peptides and amyloid plaques,” said corresponding author Jeffrey Savas, PhD, associate professor of behavioral neurology at Northwestern University Feinberg School of Medicine. “Our new results uncovered new biology while also opening doors for new drug targets.”