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

被引：36

作者：

Garcia-Alloza, Monica ^{[1
]}

Ferrara, Brian J. ^{[1
]}

Dodwell, Sarah A. ^{[1
]}

Hickey, Gregory A. ^{[1
]}

Hyman, Bradley T. ^{[1
]}

Bacskai, Brian J. ^{[1
]}

机构：

[1] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, Charlestown, MA 02129 USA

来源：

NEUROBIOLOGY OF DISEASE | 2007年 / 28卷 / 03期

关键词：

Alzheimer; immunotherapy; multiphoton; imaging; neuritic dystrophy; senile plaque; microglia;

D O I：

10.1016/j.nbd.2007.07.019

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：286 / 292

页数：7

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