Taken together, we demonstrated that early and multiple transplantations of APOE3/3-PCs or APOE3/3-PC-derived IGF2-rich ApoVs could prevent pericyte degeneration and BBB damage, and rescue cognitive decline and AD pathologies in aged APOE4/4 mice, which may represent a promising therapy strategy for APOE4-related AD and other pericyte-degeneration disease. The gene discussed is IGF2; the disease is Alzheimer disease.