Abstract
The mechanisms by which anti-Abeta antibodies clear amyloid plaques in Abeta depositing transgenic mice are unclear. In the current study, we demonstrate that inhibition of anti-Abeta antibody-induced microglial activation with anti-inflammatory drugs, such as dexamethasone, inhibits removal of fibrillar amyloid deposits. We also show that anti-Abeta F(ab')(2) fragments fail to activate microglia and are less efficient in removing fibrillar amyloid than the corresponding complete IgG. Diffuse Abeta deposits are cleared by antibodies under all circumstances. These data suggest that microglial activation is necessary for efficient removal of compact amyloid deposits with immunotherapy. Inhibition of this activation may result in an impaired clinical response to vaccination against Abeta.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / drug therapy
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Alzheimer Disease / immunology*
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / antagonists & inhibitors*
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Amyloid beta-Peptides / immunology
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Amyloid beta-Peptides / metabolism
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Animals
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Anti-Inflammatory Agents / pharmacology
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Antibodies / immunology
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Antibodies / pharmacology*
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Antibodies / therapeutic use
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Brain / drug effects
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Brain / immunology
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Brain / physiopathology
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Dexamethasone / pharmacology
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Disease Models, Animal
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Encephalitis / immunology
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Encephalitis / physiopathology
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Flurbiprofen / analogs & derivatives*
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Flurbiprofen / pharmacology
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Gliosis / immunology*
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Gliosis / metabolism
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Immunoglobulin G / immunology
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Leukocyte Common Antigens / metabolism
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Mice
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Mice, Transgenic
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Microglia / drug effects
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Microglia / immunology*
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Peptide Fragments / pharmacology
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Plaque, Amyloid / immunology*
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Plaque, Amyloid / metabolism
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Vaccines / immunology
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Vaccines / pharmacology
Substances
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(3-4-(2-fluoromethyl-(1,1'-biphenyl)-4-acetyloxy)-3-methoxyphenyl)-2-propenoic acid 4-nitrooxy butyl ester
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Amyloid beta-Peptides
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Anti-Inflammatory Agents
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Antibodies
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Immunoglobulin G
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Peptide Fragments
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Vaccines
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Flurbiprofen
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Dexamethasone
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Leukocyte Common Antigens