Journal
NEUROBIOLOGY OF DISEASE
Volume 15, Issue 1, Pages 11-20Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2003.09.015
Keywords
amyloid deposits; anti-A beta; microglia
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Funding
- NIA NIH HHS [AG20227, AG18478, AG15490] Funding Source: Medline
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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 A 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. (C) 2003 Elsevier Inc. All rights reserved.
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