CTSD and Alzheimer disease: ScRNA-seq analysis of DAM in Tg-AD and triggering receptor expressed on myeloid cells 2 (Trem2)-/- Tg-AD mice demonstrated that differentiation to DAM is a two-step process, in which Trem2-independent activation involves downregulation of the core microglia genes P2ry12, Cx3cr1 and Tmem119, and upregulation of Tyrbp, Apoe, B2m, Ctsb, and Ctsd, whereas a late-stage DAM upregulated Spp1, Axl, Ccl6, H2-D1, and genes involved in phagocytosis and lipid metabolism: Lpl, Cst7, and Cd9 [72].