TREM2 and Alzheimer disease: 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).