By activating TNFR2 in our AD mouse model, we observed a decrease in Aβ production based on lower BACE-1 levels together with a remarkable increase in Aβ uptake due to the enhanced phagocytic activity of microglia, which potentially resulted in a drastic reduction in Aβ plaque load and improvement of cognitive functions. Here, TNFRSF1B is linked to Alzheimer disease.