Alzheimer's: a decades-old FDA-approved drug may slow progression

Northwestern researchers report that amyloid-beta 42 accumulates inside synaptic vesicles and that the antiseizure drug levetiracetam reduced this peptide's formation in laboratory models; analysis of prior clinical trials showed a small delay between dementia diagnosis and death among patients who took levetiracetam.

Researchers at Northwestern University describe new laboratory and tissue findings about early steps in Alzheimer's disease and report that an existing antiseizure drug can alter those steps. The team found that the toxic peptide amyloid-beta 42 gathers inside synaptic vesicles, which are the small sacs that store neurotransmitters. In experiments with animal models and human neurons, application of levetiracetam reduced formation of amyloid-beta 42. The study links abnormal processing of the amyloid precursor protein (APP) to early peptide production and explores how shifting APP processing could affect later disease stages. Key findings: - Amyloid-beta 42 was observed to accumulate inside synaptic vesicles in the models and tissues studied. - Levetiracetam prevented neurons in animal and human laboratory models from forming amyloid-beta 42. - The researchers report that levetiracetam appears to enable APP to divert from pathways that produce amyloid-beta 42. - Analysis of existing clinical trial data found a small delay, on the order of a few years, between dementia diagnosis and death for Alzheimer's patients who took levetiracetam. - The team notes levetiracetam is rapidly broken down in the body and are developing a longer-lasting version. - Researchers plan to study genetically high-risk groups, including people with Down syndrome, where early changes appear before typical symptom onset. Summary: The report identifies a mechanism for early amyloid production in synaptic vesicles and shows that levetiracetam can reduce that production in laboratory settings. Clinical-trial analysis provided limited evidence of slower progression among patients who took the drug, and researchers say prevention would require very early intervention. The team intends to study high-risk genetic populations and to develop a longer-lasting compound based on these findings.