CTSD and Alzheimer disease: This state was first described in an Alzheimer’s disease (AD) 5xFAD mouse model, where a subset of microglia near amyloid plaques upregulated genes involved in lipid metabolism, phagocytosis, and antigen presentation (e.g., Apoe, Trem2, Axl, Lpl, Ctsd, and Cd74) while concurrently downregulating homeostatic markers such as P2ry12 and Tmem119 [128, 129].