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.
MeSH terms
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Alzheimer Disease / immunology
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Alzheimer Disease / metabolism
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Amyloid beta-Peptides / immunology*
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Amyloid beta-Peptides / pharmacology
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Animals
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Astrocytes / cytology
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Astrocytes / drug effects
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Astrocytes / immunology*
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Brain / cytology
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Brain / immunology
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Chemokine CCL2 / genetics
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Chemokine CCL2 / immunology*
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Chemokine CCL5 / genetics
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Chemokine CCL5 / immunology*
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Chemokine CXCL2
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Chemokines, CXC*
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Chemotactic Factors / genetics
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Chemotactic Factors / immunology
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Chemotaxis / drug effects
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Chemotaxis / immunology
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Gene Expression / immunology
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Growth Inhibitors / genetics
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Growth Inhibitors / immunology
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Growth Substances / genetics
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Growth Substances / immunology
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Intercellular Signaling Peptides and Proteins*
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / immunology
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Microglia / cytology
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Microglia / drug effects
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Microglia / immunology
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Monokines / genetics
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Monokines / immunology
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Neuritis / immunology
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Oligodendroglia / cytology
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Oligodendroglia / drug effects
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Oligodendroglia / immunology
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Oligonucleotide Probes
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Peptide Fragments / immunology*
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Peptide Fragments / pharmacology
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Rats
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Rats, Wistar
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Reactive Oxygen Species / immunology*
Substances
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Amyloid beta-Peptides
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Chemokine CCL2
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Chemokine CCL5
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Chemokine CXCL2
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Chemokines, CXC
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Chemotactic Factors
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Cxcl2 protein, rat
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Growth Inhibitors
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Growth Substances
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Intercellular Signaling Peptides and Proteins
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Monokines
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Oligonucleotide Probes
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Peptide Fragments
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Reactive Oxygen Species
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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amyloid beta-protein (35-25)
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amyloid beta-protein (40-1)