Yeast-derived vacuoles as potential therapeutic agents for modulating neuroinflammation in Alzheimer's disease.

Neuroinflammation is a major contributor to Alzheimer's disease (AD) pathology, including amyloid precursor protein (APP)/amyloid-beta (Aβ)-associated protein expression and Tau phosphorylation. Here, we evaluated yeast-derived vacuoles as orally deliverable bio-derived vesicular structures for modulating AD-associated neuroinflammatory responses. In lipopolysaccharide (LPS)-stimulated C6 glioma cells, vacuoles were efficiently internalized, showed minimal cytotoxicity, reduced APP/Aβ-related protein and phosphorylated Tau levels, and suppressed p38 MAPK and NF-κB signaling, including downstream inducible nitric oxide synthase expression. In aged C57BL/6 mice, oral vacuole administration reduced brain APP/Aβ-related protein, Tau, and phosphorylated Tau levels and improved histological features in the hippocampus and cortex. Although direct brain biodistribution was not detected by IVIS imaging, the observed functional changes support further investigation of vacuole-mediated gut-to-brain bioactivity. These findings suggest yeast-derived vacuoles as a promising bio-derived platform for modulating neuroinflammation in AD.