Microglial activation facilitates Aβ plaque removal following intracranial anti-Aβ antibody administration

The mechanisms by which anti-Aβ antibodies clear amyloid plaques in Aβ depositing transgenic mice are unclear. In the current study, we demonstrate that inhibition of anti-Aβ antibody-induced microglial activation with anti-inflammatory drugs, such as dexamethasone, inhibits removal of fibrillar amyloid deposits. We also show that anti-Aβ F(ab′)₂ fragments fail to activate microglia and are less efficient in removing fibrillar amyloid than the corresponding complete IgG. Diffuse Aβ 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 Aβ.