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β-amyloid, microglia, and the inflammasome in Alzheimer’s disease

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.

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Acknowledgments

Maike Gold is a postdoctoral Research Fellow of the Max Kade Foundation. Part of the work described here was supported by NIH grants NIH grants NS059005, AG032349, and AI082660 to Joseph El Khoury.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Correspondence to Joseph El Khoury.

Additional information

This article is a contribution to the Special Issue on : Role of Astrocytes and Microglia in CNS Inflammation - Guest Editor: Francisco Quintana

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Gold, M., El Khoury, J. β-amyloid, microglia, and the inflammasome in Alzheimer’s disease. Semin Immunopathol 37, 607–611 (2015). https://doi.org/10.1007/s00281-015-0518-0

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Keywords

  • Microglia
  • Macrophage
  • NLRP3 inflammasome
  • β-amyloid
  • Alzheimer’s disease