APOE4 astrocytes call the shots on neuronal α-synuclein pathology.

In this issue of Cell Stem Cell, Mesentier-Louro et al. use a multi-cellular integrated brain (miBrain) system to uncover mechanisms underlying the accumulation of neuronal α-synuclein (α-Syn) inclusions in APOE4 carriers.1 Their results suggest that APOE4 increases cholesterol levels and impairs lysosomal function in astrocytes, which release pathogenic α-Syn.