Abstract
Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism
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Amyloid beta-Peptides / metabolism*
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Amyloid beta-Peptides / pharmacology
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Animals
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CD40 Antigens / biosynthesis
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CD40 Antigens / metabolism*
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CD40 Ligand
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Cell Death
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Cells, Cultured
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Interferon-gamma / pharmacology
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Interleukins / pharmacology
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Ligands
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Membrane Glycoproteins / metabolism*
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Membrane Glycoproteins / pharmacology
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Mice
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Mice, Transgenic
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Microglia / cytology
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Microglia / immunology
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Microglia / metabolism*
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Neurons / cytology
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Peptide Fragments / pharmacology
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Phosphorylation
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Signal Transduction
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / pharmacology
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tau Proteins / metabolism
Substances
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Amyloid beta-Peptides
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CD40 Antigens
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Interleukins
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Ligands
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Membrane Glycoproteins
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Peptide Fragments
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Tumor Necrosis Factor-alpha
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amyloid beta-protein (1-42)
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tau Proteins
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CD40 Ligand
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Interferon-gamma