For decades, the battle against Alzheimer’s disease has been a game of “catch-up.” Modern treatments like lecanemab and donanemab focus on clearing away the sticky amyloid-beta plaques that have already clogged a patient’s brain. But by the time these plaques are visible on a scan, the damage is often irreversible. Now, researchers at Northwestern University have discovered that a common, inexpensive anti-seizure medication may hold the key to a different strategy: stopping the toxic proteins from being produced in the first place.
The study, recently published in the journal Science Translational Medicine, highlights levetiracetam—better known by its brand name, Keppra. First approved by the FDA in 1999 to treat epilepsy, this drug is now showing a surprising ability to disrupt the earliest molecular steps of Alzheimer’s.
The “paradoxical” discovery
For ten years, senior author Jeffrey Savas, an associate professor at Northwestern University Feinberg School of Medicine, has been investigating what goes wrong at the very beginning of the disease. His team discovered a “paradoxical stage” where presynaptic proteins begin to accumulate long before synapses are lost or dementia symptoms appear.
They found that a specific, highly toxic protein fragment called amyloid-beta 42 builds up inside synaptic vesicles—the tiny sacs neurons use to send signals. When the team treated human neurons and animal models with levetiracetam, the drug effectively blocked the formation of this toxic peptide.
According to a Northwestern University press release, this mechanism marks a shift from clearing existing plaques to preventing their initial formation.
A mechanism for brain signals
By binding to the protein SV2A during the “synaptic vesicle cycle,” the drug slows the recycling process and keeps the amyloid precursor protein (APP) on the surface of neurons longer. This prevents APP from entering internal pathways, effectively stopping it from being cut into toxic fragments.
