Anti-Seizure Drug Shows Promise in Preventing Alzheimer’s Disease

A medication long used for treating seizures may offer new hope in the fight against Alzheimer’s disease, according to a groundbreaking study from Northwestern University researchers.

Levetiracetam, approved by the FDA in 1999 under the brand name Keppra for partial-onset seizures in adults, has demonstrated the ability to prevent the formation of toxic amyloid beta peptides in the brain—protein fragments commonly associated with Alzheimer’s disease.

The findings, published in Science Translational Medicine, reveal that the medication prevented the formation of amyloid-beta 42 in both animal models and cultured human neurons. Researchers observed similar effects in post-mortem brain tissue from individuals with Down syndrome, who face heightened risk of developing Alzheimer’s.

“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,” explained Jeffrey Savas, associate professor of behavioral neurology at Northwestern University Feinberg School of Medicine and the study’s corresponding author.

The research suggests that the drug works by addressing an age-related vulnerability in the brain. According to Savas, younger brains are better equipped to avoid the pathway that produces toxic amyloid-beta 42 proteins, but this ability diminishes with age.

“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,” Savas noted.

This excess amyloid-beta 42 can trigger a cascade of damaging events, including the formation of tau “tangles”—abnormal protein clumps inside brain neurons—that ultimately kill brain cells, cause neuroinflammation, and lead to dementia symptoms.

The researchers also analyzed previous clinical data, finding that Alzheimer’s patients who happened to be taking levetiracetam for other conditions showed a “significant delay” in the progression from cognitive decline to death compared to those not taking the medication. While the researchers described the effect as “small” (on the scale of a few years), they believe it supports the drug’s potential to slow Alzheimer’s progression.

For levetiracetam to be effective as an Alzheimer’s preventative, Savas emphasized that high-risk patients would need to begin treatment “very, very early”—potentially 20 years before elevated amyloid-beta 42 levels would typically be detected.

“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,” he cautioned.

The research team is now planning to recruit participants with genetic forms of Alzheimer’s for further testing. They also acknowledge levetiracetam’s limitations, including its rapid breakdown in the body, and are working to develop an improved version that would last longer and better target the mechanism that prevents plaque formation.

As with any medication, levetiracetam comes with potential side effects. Common adverse reactions include drowsiness, weakness, dizziness, irritability, headache, loss of appetite, and nasal congestion. More serious but rarer effects can include mood and behavior changes, severe allergic reactions, skin reactions, blood disorders, and suicidal ideation.

The study had several limitations worth noting. It relied primarily on animal models and cultured cells without human clinical trials specifically testing the Alzheimer’s prevention hypothesis. Being observational in nature, the research cannot definitively prove that the medication directly caused the prevention of toxic brain proteins.

This research represents a potentially significant development in Alzheimer’s prevention strategies, particularly as the pharmaceutical industry has struggled to develop effective treatments for the disease, which affects millions worldwide. The possibility of repurposing an existing, well-studied medication could accelerate the path to clinical use if further research confirms these preliminary findings.

The study was funded by the National Institutes of Health and the Cure Alzheimer’s Fund, highlighting the significant interest in finding new approaches to combat this devastating neurodegenerative disease.