1705-APOE4 Astrocytes Drive α-Synuclein Pathology in miBrain

Paper Talk · Oct 24, 2026 · 24m

Researchers developed a multicellular human brain model called a miBrain to investigate how the APOE4 genetic variant drives neurodegenerative pathology. Their experiments revealed that APOE4 astrocytes suffer from cholesterol dysregulation and endolysosomal dysfunction, preventing them from properly degrading internalized alpha-synuclein. Instead, these impaired astrocytes process the protein into pathogenic seeds that promote neuronal alpha-synuclein aggregation and cell damage. Importantly, treatment with methyl-beta-cyclodextrin successfully reduced cholesterol levels, restored lysosomal…