Extracellular ATP is a mediator of intercellular communication and a danger signal. Release of this nucleotide activate the P2XB_7B receptor subtype which stands out for its pro-inflammatory activity. Furthermore, the P2X₇ receptor is up-regulated in a transgenic model of Alzheimer's disease and in brains from Alzheimer's patients. In this study we show that amyloid b (Ab) triggers increases in intracellular CaP^2+P ([CaP^2+P]B_iB), ATP release, IL-1b secretion and plasma membrane permeabilization in microglia from wild type but not from P2XB_7B-deleted mice. Likewise, intra hippocampal injection of Ab causes a large accumulation of IL-1b in wild-type but not in P2XB_7PB^-/-P mice. These observations suggest that Ab activates a purinergic autocrine/paracrine stimulatory loop of which the P2XB_7B receptor is an obligate component. Identification of the P2XB_7B receptor as a non-dispensable factor of Ab-mediated microglia stimulation may open new avenues for the treatment of Alzheimer's disease.