Our data showed that Klotho overexpression inhibited NLRP3 inflammasome activation and promoted Aβ clearance through an increase in M2 type microglia and the regulation of Aβ transporters in APP/PS1 mice, which effectively relieved neuroinflammation and Aβ burden and ameliorated AD‐like phenotypes. This evidence concerns the gene KL and Alzheimer disease.