The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer's disease

Marina Saresella, Francesca La Rosa, Federica Piancone, Martina Zoppis, Ivana Marventano, Elena Calabrese, Veronica Rainone, Raffaello Nemni, Roberta Mancuso, Mario Salvatore Clerici

Research output: Contribution to journalArticlepeer-review

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-1 β 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.

Original languageEnglish
Article number23
JournalMolecular Neurodegeneration
Volume11
Issue number1
DOIs
Publication statusPublished - 2016

Keywords

  • Alzheimer's disease
  • Beta amyloid
  • Inflammasome
  • Mild cognitive impairment
  • Neuroinflammation

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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