title: The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease.
abstract: BACKGROUND
  Interleukin-1 beta (IL-1β) and its key regulator, the inflammasome, are suspected to play a role in the neuroinflammation observed in Alzheimer's disease (AD); no conclusive data are nevertheless available in AD patients.
  
  
  RESULTS
  mRNA for inflammasome components (NLRP1, NLRP3, PYCARD, caspase 1, 5 and 8) and downstream effectors (IL-1β, IL-18) was up-regulated in severe and MILD AD. Monocytes co-expressing NLRP3 with caspase 1 or caspase 8 were significantly increased in severe AD alone, whereas those co-expressing NLRP1 and NLRP3 with PYCARD were augmented in both severe and MILD AD. Activation of the NLRP1 and NLRP3 inflammasomes in AD was confirmed by confocal microscopy proteins co-localization and by the significantly higher amounts of the pro-inflammatory cytokines IL-1β and IL-18 being produced by monocytes. In MCI, the expression of NLRP3, but not the one of PYCARD or caspase 1 was increased, indicating that functional inflammasomes are not assembled in these individuals: this was confirmed by lack of co-localization and of proinflammatory cytokines production.
  
  
  CONCLUSIONS
  The activation of at least two different inflammasome complexes explains AD-associated neuroinflammation. Strategies targeting inflammasome activation could be useful in the therapy of AD.
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. msaresella@dongnocchi.it.
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. flarosa@dongnocchi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: La Rosa
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. fpiancone@dongnocchi.it.
authors.forename: Federica
authors.initials: F
authors.lastname: Piancone
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. mzoppis@dongnocchi.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Zoppis
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. imarventano@dongnocchi.it.
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. ecalabrese@dongnocchi.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Calabrese
authors.affiliation: Departments of Biomedical and Clinical Sciences "Luigi Sacco", University of Milano, 20100, Milan, Italy. veronica.rainone@unimi.it.
authors.forename: Veronica
authors.initials: V
authors.lastname: Rainone
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. rnemni@dongnocchi.it.|Departments of Physiopathology and Transplants, University of Milano, 20100, Milan, Italy. rnemni@dongnocchi.it.
authors.forename: Raffaello
authors.initials: R
authors.lastname: Nemni
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. rmancuso@dongnocchi.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Mancuso
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121, Milan, Italy. mario.clerici@unimi.it.|Departments of Physiopathology and Transplants, University of Milano, 20100, Milan, Italy. mario.clerici@unimi.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C427903:NLRP1 protein, human; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D020170:Caspase 1