AD-associated fibrillar Aβ was the first misfolded protein shown to act as an NLRP3-activating agent, eliciting IL-1β secretion and the formation of oligomerized ASC specks in lipopolysaccharide-primed primary mouse microglia through interactions with pattern recognition receptors (PRRs), CD36, TLR2, RAGE, and TREM2 (Fig. 1B) (22, 23, 24, 25, 26, 27, 28, 29). The gene discussed is NLRP3; the disease is Alzheimer disease.