Targeting TREM2-APOE signaling eliminated pro-inflammatory macrophages (Ly6C+) in Alzheimer's disease mice, restored the homeostatic signature of microglia, reduced inflammation, ameliorated Aβ deposition and Tau pathology, and prevented neuronal death in an acute model of neurodegeneration 36,52. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.