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

Abstract

Amyloid-β (Aβ) 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 Aβ probably results in part from microglia-mediated inflammation, it can be microglia independent. Therefore, establishing the role of microglia in Aβ clearance is important for the treatment of AD. We analyzed the effects of direct microglia activation and inhibition on antibody-mediated Aβ clearance. Robust microglia activation with interferon-γ led to modest Aβ clearance alone but did not potentiate antibody-mediated clearance. Microglia elimination/inactivation with immunotoxin or minocycline only partially limited antibody-induced Aβ clearance suggesting that although there is a role for microglia in Aβ clearance, it does not account for the majority of the effect observed after anti-Aβ antibody treatment.

Keywords

• Alzheimer
• Immunotherapy
• Multiphoton
• Imaging
• Neuritic dystrophy
• Senile plaque