APOE and Alzheimer disease: The elevated MMP9 levels in AD brains and the reduced ability of apoE4 to modulate MMP9 disposition in our prior studies [18] prompted us to investigate the therapeutic value of modulating MMP9 activity in E4FAD transgenic animals, an AD mouse model expressing five familial AD (FAD) mutations (5xFAD mice) and homozygous for the human APOE4 gene.