β-amyloid, Microglia, and the Inflammasome in Alzheimer's Disease

Semin Immunopathol. 2015 Nov;37(6):607-11. doi: 10.1007/s00281-015-0518-0. Epub 2015 Aug 7.

Abstract

There is extensive evidence that accumulation of mononuclear phagocytes including microglial cells, monocytes, and macrophages at sites of β-amyloid (Aβ) deposition in the brain is an important pathological feature of Alzheimer's disease (AD) and related animal models, and the concentration of these cells clustered around Aβ deposits is several folds higher than in neighboring areas of the brain [1-5]. Microglial cells phagocytose and clear debris, pathogens, and toxins, but they can also be activated to produce inflammatory cytokines, chemokines, and neurotoxins [6]. Over the past decade, the roles of microglial cells in AD have begun to be clarified, and we proposed that these cells play a dichotomous role in the pathogenesis of AD [4, 6-11]. Microglial cells are able to clear soluble and fibrillar Aβ, but continued interactions of these cells with Aβ can lead to an inflammatory response resulting in neurotoxicity. Inflammasomes are inducible high molecular weight protein complexes that are involved in many inflammatory pathological processes. Recently, Aβ was found to activate the NLRP3 inflammasome in microglial cells in vitro and in vivo thereby defining a novel pathway that could lead to progression of AD [12-14]. In this manuscript, we review possible steps leading to Aβ-induced inflammasome activation and discuss how this could contribute to the pathogenesis of AD.

Keywords: Alzheimer’s disease; Macrophage; Microglia; NLRP3 inflammasome; β-amyloid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / immunology*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Brain / cytology
  • Brain / immunology*
  • Brain / pathology
  • Carrier Proteins / immunology*
  • Cytokines / metabolism
  • Humans
  • Inflammasomes
  • Macrophages / immunology
  • Microglia / immunology
  • Monocytes / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Phagocytosis

Substances

  • Amyloid beta-Peptides
  • Carrier Proteins
  • Cytokines
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human