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

Mol Neurodegener. 2016 Mar 3;11:23. doi: 10.1186/s13024-016-0088-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Alzheimer Disease / metabolism*
  • Apoptosis Regulatory Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Caspase 1 / metabolism
  • Cells, Cultured
  • Humans
  • Inflammasomes / metabolism*
  • Interleukin-1beta / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP1 protein, human
  • NLRP3 protein, human
  • Reactive Oxygen Species
  • Caspase 1