A common anti-seizure drug, levetiracetam, is showing early promise as a way to block the production of the toxic amyloid-beta 42 peptide linked to Alzheimer’s disease, according to a recent Northwestern University study. Researchers saw this effect in animal models, cultured human neurons and post-mortem brain tissue from people with Down syndrome, a group at high risk for Alzheimer’s. The work points to a preventive strategy rather than plaque removal, but it relies on lab models and observational human data, so human trials are still needed. The team is working on longer-lasting versions of the drug and plans targeted testing in people with genetic risk.
Levetiracetam was approved by the FDA in 1999 under the brand name Keppra for partial-onset seizures and its use has broadened since then to treat various seizure types and age groups. Its safety profile is well documented from decades of epilepsy care, which makes researchers curious about repurposing it for brain disorders beyond seizures. The drug’s mechanism of action is not fully understood in the context of Alzheimer’s, but this new work points to a specific pathway that could be exploited.
The study found levetiracetam blocks the pathway that leads to the formation of amyloid-beta 42, a particularly toxic fragment that seeds amyloid plaques associated with Alzheimer’s. That prevention was observed in animal experiments and in human neurons grown in the lab, suggesting the effect is not limited to one model system. The researchers also examined post-mortem brain tissue from people with Down syndrome, where the protective effect was evident, reinforcing the biological signal.
“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, associate professor of behavioral neurology at Northwestern University Feinberg School of Medicine, in a press release. “Our new results uncovered new biology while also opening doors for new drug targets.” Those lines point to a different strategy: stop toxic proteins before plaques form rather than trying to remove plaques later.
The team explains that younger brains naturally avoid the pathway that produces amyloid-beta 42, but aging weakens that protection, making some neurons more likely to generate the peptide. “This is not a statement of disease; this is just a part of aging. But in brains developing Alzheimer’s, too many neurons go astray, and that’s when you get amyloid-beta 42 production,” the paper notes. If the cascade begins decades before symptoms, earlier intervention would be essential for prevention.
That timing matters because levetiracetam looks unlikely to reverse established dementia. “You couldn’t take this when you already have dementia, because the brain has already undergone a number of irreversible changes and a lot of cell death,” the researcher noted. In short, the drug could be a preventive tool for high-risk people, not a cure for late-stage disease where neuronal loss is already severe.
The authors also mined existing clinical data to see whether people with Alzheimer’s who happened to be on levetiracetam for seizures had different outcomes. They reported a “significant delay” in the interval from cognitive decline to death among those taking the drug compared with those who were not, though the effect size was modest. “Although the magnitude of change was small (on the scale of a few years), this analysis supports the positive effect of levetiracetam to slow the progression of Alzheimer’s pathology,” Savas said.
Despite the encouraging signals, the study has clear limitations: it leaned heavily on animal models and cultured cells and did not include new human clinical trials. The observational nature of the human data means the results do not prove cause and effect, and the authors acknowledge the need for carefully controlled testing. They also point out that levetiracetam breaks down quickly in the body, which limits its practicality for long-term prevention.
To address that weakness the team is developing modified molecules that last longer and more precisely target the mechanism that stops amyloid-beta 42 production. If those candidates perform well in safety testing, they could enter trials focused on people with genetic forms of Alzheimer’s or other high-risk groups. The push is to move from a lab finding to a preventive therapy that can be given years before symptoms emerge.
The drug’s known side effects include drowsiness, weakness, dizziness, irritability, headache, loss of appetite and nasal congestion, and there are documented risks of mood and behavior changes such as anxiety, depression, agitation and aggression. Rare but serious reactions can include severe allergic responses, skin reactions, blood disorders and suicidal thoughts, so any preventive use would require careful risk-benefit discussion. The study received funding support from the National Institutes of Health and the Cure Alzheimer’s Fund as the team advances toward more targeted candidates for testing.
