APOE and Alzheimer disease: In experiments in which the APOE4 gene was edited with CRISPR/Cas9 and converted to APOE3 in iPSCs from patients with sporadic AD, tau protein phosphorylation and ERK1/2 phosphorylation were weaker in edited neurons compared with unedited APOE4 neurons, and edited neurons showed isoform-dependent phosphorylated tau protein release decreased (Lin et al., 2018; Khan et al., 2025).