As will be described, recent work with hiPSC-based models has underscored that human and rodent glia differ significantly in terms of morphology, function, and gene expression profiles (Preman et al, 2021), particularly in the lack of APOE ε4-driven lipid metabolic dysregulation pathways now generally accepted to contribute to AD (TCW et al, 2022). This evidence concerns the gene APOE and Alzheimer disease.