Linking glycosphingolipids to Alzheimer's amyloid-ß: extracellular vesicles and functional plant materials

Glycosphingolipids (GSLs) are a specialized class of membrane lipids composed of a ceramide and a carbohydrate head group. GSLs are localized in cell membranes and were recently found to be enriched in the membrane of neuron-derived exosomes, which are a type of extracellular vesicle. Our studies demonstrated that exosomal GSLs may be associated with the amyloid-ß (Aß) peptide, a principal agent of Alzheimer's disease (AD), and act to clear Aß by transporting Aß into brain phagocytic microglia. In this review, we summarize and discuss the function of exosomal GSLs in Aß homeostasis in AD pathology. Improvement in Aß clearance is a potent strategy for AD prevention and therapy. Dietary glucosylceramides (GlcCer) isolated from plants are absorbed into the body as various metabolites, including ceramides. Our recent work demonstrated that dietary GlcCer accelerates neuronal exosome production, which facilitates Aß clearance in mice. Furthermore, studies of AD model mice and human clinical trials have found that oral administration of plant-type GlcCer attenuates the Aß burden in the brain. We also introduce the development of plant-type GlcCer as functional food materials to prevent AD.