A central role for astrocytes in the inflammatory response to beta-amyloid; chemokines, cytokines and reactive oxygen species are produced

M Johnstone, A J Gearing, K M Miller

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease (AD) is the commonest form of adult onset dementia and is characterised neuropathologically by the accumulation of plaques containing beta-amyloid (A beta) fibrils, reactive astrocytes, activated microglia, and leukocytes. A beta plays a role in the pathology of AD by directly causing neuronal cytotoxicity and stimulating microglia to secrete cytokines and reactive oxygen species (ROS) which also damage neurons. Here, we demonstrate that A beta activates astrocytes and oligodendrocytes (the most common cell types in the brain) to produce chemokines, in particular MCP-1 and RANTES, which serve as potent in vitro microglial and macrophage chemoattractants. Furthermore, we have shown that A beta activates astrocytes to upregulate pro-inflammatory cytokine expression and enhances the production of ROS. We propose therefore that A beta-mediated astrocyte activation initiates an inflammatory cascade which could be targeted for therapeutic intervention in AD.

Original languageEnglish
Pages (from-to)182-93
Number of pages12
JournalJournal of Neuroimmunology
Volume93
Issue number1-2
Publication statusPublished - 1 Jan 1999

Keywords

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Animals
  • Astrocytes
  • Brain
  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokine CXCL2
  • Chemokines, CXC
  • Chemotactic Factors
  • Chemotaxis
  • Gene Expression
  • Growth Inhibitors
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Macrophages
  • Microglia
  • Monokines
  • Neuritis
  • Oligodendroglia
  • Oligonucleotide Probes
  • Peptide Fragments
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species

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