The accumulation of amyloid-β (Aβ) in the brain is believed to have a pivotal role in Alzheimer disease (AD) pathology. Kumar et al. now provide in vivo evidence that Aβ may also perform a protective antimicrobial function. Genetically modified AD mouse models expressing Aβ were protected from Salmonella enterica subsp. enterica serovar Typhimurium meningitis infection, with mice exhibiting rapid seeding and accelerated Aβ deposition following exposure. Aβ expression in nematodes and cultured mammalian cells similarly increased host resistance to Candida albicans infection. The protective effects of Aβ appeared to be mediated by agglutination and entrapment of microbes by Aβ fibrils.