APOE and Alzheimer disease: Research involving AD mouse models and human-induced pluripotent stem cells has demonstrated that the apoE4 isoform not only increases Aβ load in the brain interstitial fluid, but also shows distinctive cellular behaviors, with neurons exhibiting increased synapse numbers and Aβ42 secretion, while astrocytes display reduced Aβ uptake and increased cholesterol accumulation, highlighting the isoform’s unique impact on amyloid pathology (Liu C. C. et al., 2017; Huynh et al., 2017; Lin et al., 2018).