It is likely that P2X4 belongs to the so-called DAM [39], a specific microglial population that is characterized by the specific expression of subset of genes, including several known AD risk factor such as Trem2 and ApoE. Our data show a strong co-localization of P2X4 and ApoE in plaque-associated microglia, in both mice and human AD patients, and in a recent study using mass spectrometry to identify deregulated proteins in microglia, an increase of P2X4 was observed in two mouse models of AD (APP/PS1 and APP-NL-G-F) [52]. This evidence concerns the gene PSEN1 and Alzheimer disease.