Copper also activates the secretion of NO, TNF-α and IL-6 by M1-type microglia.[60] Yi Huang’s study showed that TNF-α binding to TNFR leads to activation of NF-κB and subsequent initiation of NLRP3.[22] Studies have shown that TNF-α signaling exacerbates Aβ deposition and tau protein formation in vivo and that effective TNF-α inhibitors (etanercept) have the potential to improve cognitive performance in AD patients.[61,62]. This evidence concerns the gene NFKB1 and Alzheimer disease.