A novel genetic approach to specifically target and manipulate plaque‐associated microglia in mice

Within the Alzheimer’s disease (AD) brain, microglia surround extracellular plaques and mount a chronic inflammatory response. These plaque‐associated microglia (PAMs) are characterized by specific disease‐associated gene expression signatures, including Apoe, Cst7, Trem2, Clec7a, Itgax, and Csf1. Data from animal models of AD have identified that PAMs play critical roles in plaque formation and plaque compaction, but also contribute to synaptic and neuronal dysfunction and loss. To better understand the role of microglia in AD, we need precise models which directly target specific subsets of microglia, however; no such model currently exists. Here, we developed a novel genetic cre‐recombinase approach to specifically target and manipulate PAMs in AD mouse models. We identified that of PAM‐identified genes Cst7 shows no expression in the homeostatic mouse brain and is specifically and highly expressed in PAMs.