An inexpensive FDA-approved epilepsy drug could block toxic proteins decades before symptoms appear, reframing prevention in brain aging.
In Alzheimer’s, toxic protein fragments accumulate in the brain, plaques form, neurons die and memory fades. The pharmaceutical response has largely been to clean up those plaques once they appear. But what if the more powerful move is not cleaning up the damage, but preventing it?
Scientists at Northwestern University say they may have found a way to do exactly that. In a new study published in Science Translational Medicine, researchers report that levetiracetam, a widely prescribed anti-seizure medication already approved by the US Food and Drug Administration (FDA), can block the production of a particularly toxic protein linked to Alzheimer’s disease [1].
Unlike recently approved Alzheimer’s therapies such as lecanemab and donanemab, which are designed to remove amyloid plaques that have already formed, levetiracetam appears to intervene much earlier in the process. Instead of clearing the wreckage, it may prevent the crash.
Alzheimer’s is strongly associated with the buildup of amyloid-beta 42, a sticky protein fragment that can clump together and eventually form plaques. This fragment is produced when a larger, otherwise useful protein (amyloid precursor protein, or APP) is processed in a particular way inside brain cells.
APP is not a villain; it is essential for healthy brain development and communication between neurons. But under certain conditions, especially as we age, APP can be routed through a pathway that generates amyloid-beta 42.
The team discovered that this toxic fragment accumulates inside synaptic vesicles – tiny sacs neurons use to send chemical messages to each other. Think of synaptic vesicles as delivery trucks constantly moving in and out of a warehouse. Every thought, memory or sensation depends on this delivery system running smoothly.
Levetiracetam works by subtly slowing part of that delivery cycle. The drug attaches to a protein called SV2A and delays the recycling of vesicle components. That delay keeps APP on the surface of the neuron longer, steering it away from the internal processing route that produces amyloid-beta 42.
It is less about shutting something down and more about rerouting traffic. A small detour with potentially large consequences.
“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 corresponding author Dr Jeffrey Savas, associate professor of behavioral neurology at Northwestern University Feinberg School of Medicine [2]. “Our new results uncovered new biology while also opening doors for new drug targets.”
One of the most striking implications of the research is timing. Savas explained that middle-aged brains usually maintain the ability to steer proteins away from biological pathways that could cause harm.
“As we age, that protective ability gradually weakens. 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. And then it’s tau (or ‘tangles’), and then it’s dead cells, then dementia, then neuroinflammation – and then it’s too late,” he said.
The message is blunt: by the time memory loss is obvious, much of the biological cascade is already well underway.
Savas emphasized that prevention would likely require intervention “very, very early,” potentially as early as 20 years before current diagnostic tests detect even mildly elevated amyloid levels. He explained that the treatment could not be administered to those already living with dementia, as the brain had already undergone several irreversible changes and significant cell death.
Because levetiracetam has been prescribed for epilepsy for decades, researchers were able to look beyond lab models and into existing medical records. Using data from the National Alzheimer’s Coordinating Center, they compared outcomes among Alzheimer’s patients who had taken levetiracetam with those who used other anti-seizure medications or none at all.
Patients on levetiracetam experienced a meaningful delay between cognitive decline diagnosis and death compared with other groups. The effect size was modest, measured in a few years, but in a disease that steadily erodes independence, even incremental gains are meaningful.
“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.
The team also examined brain tissue from individuals with Down syndrome who died in their 20s or 30s from unrelated causes. More than 95% of people with Down syndrome develop early-onset Alzheimer’s by around age 40 because the APP gene exists in three copies in their cells.
By studying these brains before symptoms appeared, researchers observed early accumulations of presynaptic proteins, changes that precede synapse loss and dementia.
That possibility raises both hope and difficult questions. How early is too early? Who qualifies as high risk? And what does it mean to medicate someone decades before symptoms might appear?
Levetiracetam is not a perfect solution. It is cleared from the body relatively quickly, and researchers are now working on improved versions that last longer and more precisely target the pathway involved. Still, protecting the aging brain may require acting long before decline is visible.
Longevity.Technology: This is a philosophical shift. Extending lifespan without safeguarding cognitive function risks prolonging frailty. If aging gradually erodes the brain’s ability to keep proteins on safe pathways, then supporting that resilience may be central to extending healthspan.
Prevention demands patience, better risk prediction and a willingness to intervene early. It also demands a cultural shift toward thinking about brain aging the way we now think about cholesterol or blood pressure – something to monitor and manage long before crisis hits.
Photograph shows corresponding author Jeffrey Savas in discussion with members of his lab. Photograph courtesy of Northwestern University Feinberg School of Medicine
[1] https://www.science.org/doi/10.1126/scitranslmed.adp3984
[2] https://scitechdaily.com/fda-approved-seizure-drug-may-stop-alzheimers-before-it-starts/
