APOE and Alzheimer disease: Moreover, the protein–protein interaction network showed that IGFBP3 directly interacts with the enriched genes of AD patients and APOE ε4-expressing AD patient iNs at the Aβ early-seeding stage (Fig. 4g), indicating that IGFBP3 might functionally mediate the molecular pathology of sporadic AD with APOE ε4 expression at the Aβ early-seeding stage.