The NALP3 inflammasome is involved in the innate immune response to amyloid-β

Abstract

The events leading to the inflammation and tissue damage associated with Alzheimer's disease are unclear. Golenbock and colleagues now show that amyloid-β activates the NALP3 inflammasome, which triggers the release of proinflammatory and neurotoxic factors. The fibrillar peptide amyloid-β (Aβ) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1β (IL-1β) is a key cytokine in the inflammatory response to Aβ. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the release of IL-1β. Here we identify the NALP3 inflammasome as a sensor of Aβ in a process involving the phagocytosis of Aβ and subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1β pathway was essential for the microglial synthesis of proinflammatory and neurotoxic factors, and the inflammasome, caspase-1 and IL-1β were critical for the recruitment of microglia to exogenous Aβ in the brain. Our findings suggest that activation of the NALP3 inflammasome is important for inflammation and tissue damage in Alzheimer's disease.