By integrating comprehensive network analyses of microglial transcriptomic datasets with validation studies, we have developed a framework of microglial activation states in AD (Fig. 10) that allowed us to predict and confirm molecularly distinct and functionally divergent pro-inflammatory and anti-inflammatory profiles within DAM in AD mouse models, both of which emerge down-stream of the Trem2 immune checkpoint [9]. This evidence concerns the gene TREM2 and Alzheimer disease.