APOE4 causes widespread molecular and cellular alterations associated with Alzheimer's disease phenotypes in human iPSC-derived brain cell types

Abstract summary

Used iPSC-derived brain cells to map the transcriptomic and cellular consequences of APOE4. In microglia-like cells, APOE4 disrupts lipid metabolism, impairs phagocytosis, and increases inflammatory gene expression. Targeted correction of APOE4 to APOE3 rescues these phenotypes, establishing APOE4's direct microglial toxicity.

Evidence labels

Therapeutic relevance

Establishes APOE4-to-APOE3 conversion as a therapeutic strategy and identifies downstream microglial pathways as intervention targets.