Microglial activation facilitates Abeta plaque removal following intracranial anti-Abeta antibody administration.
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.
Wilcock
Donna M
DM
Department of Pharmacology, Alzheimer's Research Laboratory, University of South Florida, Tampa, FL 33612, USA.
Munireddy
Sanjay K
SK
Rosenthal
Arnon
A
Ugen
Kenneth E
KE
Gordon
Marcia N
MN
Morgan
Dave
D
D000544:Alzheimer Disease / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology / Q000503:physiopathology; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D005911:Gliosis / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology; D058225:Plaque, Amyloid / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000276:immunology / Q000494:pharmacology
C450321:(3-4-(2-fluoromethyl-(1,1'-biphenyl)-4-acetyloxy)-3-methoxyphenyl)-2-propenoic acid 4-nitrooxy butyl ester; D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D000906:Antibodies; D007074:Immunoglobulin G; D010446:Peptide Fragments; D014612:Vaccines; D005480:Flurbiprofen; D003907:Dexamethasone; D017493:Leukocyte Common Antigens