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

West, Nicole R; Tcw, Julia · Cell Stem Cell · 2026

basic_science · Level V

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Abstract

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.<sup>1</sup> Their results suggest that APOE4 increases cholesterol levels and impairs lysosomal function in astrocytes, which release pathogenic α-Syn.

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