AD-linked R47H-TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation

We identified enrichment of a disease-enhancing, proinflammatory subpopulation of microglia in human AD patient brains with the R47H-TREM2 mutation, and uncovered that enhanced Akt signaling in microglia underlies the proinflammatory cytokine state and synaptic toxicity in our R47H-TREM2 tauopathy mouse model. Overall design: Droplet-based single nuclear RNA sequencing of mouse hippocampus with and without the TREM2-R47H mutation and MK-2206 treatment.