A decades-old anti-seizure drug, levetiracetam, is showing promise in preventing the formation of toxic proteins associated with Alzheimer’s disease, according to research published February 11 in Science Translational Medicine. The findings, stemming from work at Northwestern University’s Feinberg School of Medicine, identify a specific mechanism by which the drug may halt the progression of the disease before the onset of irreversible damage.
Scientists have long understood that Alzheimer’s is characterized by the accumulation of toxic proteins in the brain, but pinpointing when and where these proteins start to amass has remained elusive. The Northwestern team discovered that a particularly harmful protein fragment, amyloid-beta 42, accumulates inside synaptic vesicles – the tiny structures within neurons responsible for transmitting signals.
When levetiracetam, commonly sold under the brand name Keppra, was applied to animal models, human neurons, and brain tissue from high-risk patients, it prevented the formation of amyloid-beta 42, the research showed. “While many of the Alzheimer’s drugs currently on the market 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 Jeffrey Savas, associate professor of behavioral neurology at Northwestern’s Feinberg School of Medicine.
The study reveals that levetiracetam alters synaptic vesicle recycling, influencing how the amyloid precursor protein (APP) is processed. Incorrectly degraded proteins accumulate within the synaptic space, leading to the formation of amyloid-beta 42. The drug appears to promote the “good” degradation of APP, directing it to the cell membrane where it is more readily captured by synaptic vesicles. In transgenic mice engineered to express an aggressive form of amyloid pathology, levetiracetam restored the synaptic vesicle cycle, resulting in a significant reduction in disease symptoms.
Researchers emphasize that targeting these early, presynaptic alterations represents a crucial opportunity for therapeutic intervention. “These alterations intervene before the accumulation of Aβ42 in the synaptic lumen causes irreversible effects,” the study authors wrote. The research does not yet address the role of the Tau protein, another key component in Alzheimer’s pathology, though future studies may explore levetiracetam’s potential impact on Tau accumulation.
The findings have spurred ongoing clinical trials to evaluate the efficacy of levetiracetam in slowing Alzheimer’s progression. The drug’s existing FDA approval and low cost make it an attractive candidate for repurposing, offering a potentially accessible and affordable treatment option for a disease affecting nearly 7 million Americans, with millions more likely undiagnosed, according to recent estimates.
