title: The NALP3 inflammasome is involved in the innate immune response to amyloid-beta.
abstract: The fibrillar peptide amyloid-beta (A beta) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1 beta (IL-1 beta) is a key cytokine in the inflammatory response to A beta. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the release of IL-1 beta. Here we identify the NALP3 inflammasome as a sensor of A beta in a process involving the phagocytosis of A beta and subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1 beta pathway was essential for the microglial synthesis of proinflammatory and neurotoxic factors, and the inflammasome, caspase-1 and IL-1 beta were critical for the recruitment of microglia to exogenous A beta in the brain. Our findings suggest that activation of the NALP3 inflammasome is important for inflammation and tissue damage in Alzheimer's disease.
authors.affiliation: Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Annett
authors.initials: A
authors.lastname: Halle
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.forename: Gabor C
authors.initials: GC
authors.lastname: Petzold
authors.forename: Cameron R
authors.initials: CR
authors.lastname: Stewart
authors.forename: Brian G
authors.initials: BG
authors.lastname: Monks
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinheckel
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.forename: Eicke
authors.initials: E
authors.lastname: Latz
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Moore
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D002352:Carrier Proteins / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000502:physiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human