At the heart of the new discovery is amyloid precursor protein (APP), a protein that plays important roles in brain development and synaptic formation. Abnormal processing of APP can lead to the production of amyloid‑beta peptides, which play a central role in the development of Alzheimer’s disease. The scientists found that how APP is trafficked also controls whether a neuron forms amyloid-beta 42.
During the synaptic vesicle cycle — a fundamental process that underlies every thought, movement, memory or sensation — levetiracetam binds to a protein called SV2A. This interaction slows down a step in which neurons recycle synaptic vesicle components from the cell’s surface. By pausing this recycling process, the drug enables APP to remain on the cell’s surface longer, diverting it away from the pathway that produces toxic amyloid‑beta 42 proteins.
“In our 30s, 40s and 50s, our brains are generally able to steer proteins away from harmful pathways,” the author said. “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.”
To effectively prevent Alzheimer’s symptoms, high-risk individuals would need to begin taking levetiracetam “very, very early,” the author said, possibly up to 20 years before the new FDA-approved Alzheimer’s disease test would even capture mildly elevated levels of amyloid-beta 42.
“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 author said.
Leveraging its status as an FDA-approved and widely used drug, the team mined existing human clinical data to investigate whether Alzheimer’s patients who took levetiracetam experienced slowed cognitive decline. They obtained clinical data from the National Alzheimer’s Coordinating Center and conducted a correlative analysis, finding that Alzheimer’s patients who took levetiracetam were associated with a significant delay from the diagnosis of cognitive decline to death compared to those taking lorazepam or no/other anti-epileptic drugs. ScienceMission sciencenewshighlights.
