This three-year $3.16 million project grant from the National Institutes of Health's National Institute on Aging will fund research into the role of ceramide in extracellular vesicle-mediated neurodegenerative disease processes like Alzheimer's. Specifically, the University of Kentucky Research Foundation will investigate how ceramide contributes to the formation and toxicity of astrocyte-derived extracellular vesicles known as "astrosomes" that bind to amyloid-beta, a pathological protein in Alzheimer's disease.
The researchers will utilize novel mouse models, analytical techniques and drugs to better understand sex-specific differences in astrosome formation and toxicity, with the goal of identifying ceramide metabolism enzymes that could be targeted to interfere with astrosome production in astrocytes and mitigate their neurotoxic effects. Outcomes may provide insights applicable to tau protein pathology as well. Ultimately, the project aims to generate knowledge leading to new Alzheimer's therapies effective for both sexes by preventing astrosome-mediated neurodegeneration through inhibition of ceramide pathways.
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