Although our results do not directly demonstrate a link between the increase of microglial ApoE in P2X4-deficient mice and the reduction of sAß or the attenuation of memory dysfunctions, the specific upregulation of P2X4 receptors in plaque-associated microglia and its role in ApoE degradation strongly support the involvement of this receptor to AD behavioral deficits. This evidence concerns the gene APOE and Alzheimer disease.