A limited role for microglia in antibody mediated plaque clearance in APP mice

Amyloid-beta (A beta) accumulation in senile plaques is a hallmark of Alzheimer's disease (AD). Immunotherapy is a leading approach for amyloid clearance, despite the early termination of the Elan clinical trial with active immunization due to a few cases of meningoencephalitis. The mechanisms of immunotherapy-mediated amyloid clearance and this deleterious side effect are largely unknown. While clearance of A beta probably results in part from microglia-mediated inflammation, it can be microglia independent. Therefore, establishing the role of microglia in A beta clearance is important for the treatment of AD. We analyzed the effects of direct microglia activation and inhibition on antibody-mediated A beta clearance. Robust microglia activation with interferon-gamma led to modest A beta clearance alone but did not potentiate antibody-mediated clearance. Microglia elimination/inactivation with immunotoxin or minocycline only partially limited antibody-induced A beta clearance suggesting that although there is a role for microglia in A beta clearance, it does not account for the majority of the effect observed after anti-A beta antibody treatment. (C) 2007 Elsevier Inc. All rights reserved.