open access

https://hdl.handle.net/2115/76594

Plant sphingolipids promote extracellular vesicle release and alleviate amyloid-beta pathologies in a mouse model of Alzheimer's disease

英語

2019-11-14

Nature Publishing Group

Scientific reports

9

16827

The accumulation of amyloid-beta protein (A beta) in brain is linked to the early pathogenesis of Alzheimer's disease (AD). We previously reported that neuron-derived exosomes promote A beta clearance in the brains of amyloid precursor protein transgenic mice and that exosome production is modulated by ceramide metabolism. Here, we demonstrate that plant ceramides derived from Amorphophallus konjac, as well as animal-derived ceramides, enhanced production of extracellular vesicles (EVs) in neuronal cultures. Oral administration of plant glucosylceramide (GlcCer) to APP overexpressing mice markedly reduced A beta levels and plaque burdens and improved cognition in aY-maze learning task. Moreover, there were substantial increases in the neuronal marker NCAM-1, L1CAM, and A beta in EVs isolated from serum and brain tissues of the GlcCer-treated AD model mice. Our data showing that plant ceramides prevent A beta accumulation by promoting EVs-dependent A beta clearance in vitro and in vivo provide evidence for a protective role of plant ceramides in AD. Plant ceramides might thus be used as functional food materials to ameliorate AD pathology.

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2045-2322