This review will show the interaction between SP and NK-1R on microglia activates NF-κB signaling to exacerbate the progression of AD disease and discuss the following aspects: regulating pro-inflammatory cytokines and increasing Aβ accumulation, promoting AD-related neuroinflammation, and aggravating microglia-mediated tau proliferation and toxicity. This evidence concerns the gene NFKB1 and Alzheimer disease.