ISG15 and Alzheimer disease: At the genetic level, there were 11 genes which have been shown as AD-driven regulators of MDD, including eight MDD promoters (TNF, IL33, NPPB, CRH, IL6, IL4, AGER, and ISG15) and three MDD inhibitors (BMP7, USP46, and AR), as shown in Figures 2, 3.