To determine whether IGFBP3 functionally contributes to APOE ε4-associated AD phenotypes during Aβ-seeding stage, we generated shRNA lentivirus against IGFBP3 and initially confirmed the differential expression of IGFBP3 through RT-PCR and Western blot analysis (Fig. 5c, d; Fig. S9b). The gene discussed is APOE; the disease is Alzheimer disease.