Astrocytic expression of the Alzheimer's disease β-secretase (BACE1) is stimulus-dependent
Astrocytic expression of the Alzheimer's disease β-secretase (BACE1) is stimulus-dependent
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DOI：
10.1002/glia.10178
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发表时间：
2003-01-15
期刊：
影响因子：
6.2
通讯作者：
Rossner, S
中科院分区：
文献类型：
--
作者：
Hartlage-Rübsamen, M;Zeitschel, U;Rossner, S
β位点APP切割酶（BACE 1）是产生β淀粉样肽的先决条件，β淀粉样肽会在阿尔茨海默病患者的大脑中引起脑血管和脑实质β淀粉样沉积。BACE 1在人类和实验动物如小鼠和大鼠的大脑中神经元表达。此外，我们最近表明，BACE 1蛋白表达的反应性星形胶质细胞在接近β-淀粉样蛋白斑块的老年转基因Tg 2576小鼠，过表达携带双突变K670 N-M671 L的人淀粉样蛋白前体蛋白的大脑。为了解决星形胶质细胞BACE 1表达是否是由β-淀粉样蛋白斑块特异性触发的事件，或者胶质细胞激活是否通过其他机制也诱导BACE 1表达的问题，我们使用了六种不同的实验策略来急性或慢性激活脑胶质细胞。通过免疫荧光双标记和共聚焦激光扫描显微镜对脑切片进行BACE 1和胶质细胞标记物的表达处理。在所研究的任何病变范例中，阿米巴样或分支表型的活化小胶质细胞均未检测到BACE 1蛋白的表达。相反，BACE 1表达的反应性星形胶质细胞是明显的慢性，但不是在急性模型的胶质增生。此外，我们观察到BACE 1免疫反应性星形胶质细胞接近β-淀粉样蛋白斑块在老年Tg 2576小鼠和阿尔茨海默病患者的大脑。
The beta-site APP-cleaving enzyme (BACE1) is a prerequisite for the generation of beta-amyloid peptides, which give rise to cerebrovascular and parenchymal beta-amyloid deposits in the brain of Alzheimer's disease patients. BACE1 is neuronally expressed in the brains of humans and experimental animals such as mice and rats. In addition, we have recently shown that BACE1 protein is expressed by reactive astrocytes in close proximity to beta-amyloid plaques in the brains of aged transgenic Tg2576 mice that overexpress human amyloid precursor protein carrying the double mutation K670N-M671L. To address the question whether astrocytic BACE1 expression is an event specifically triggered by beta-amyloid plaques or whether glial cell activation by other mechanisms also induces BACE1 expression, we used six different experimental strategies to activate brain glial cells acutely or chronically. Brain sections were processed for the expression of BACE1 and glial markers by double immunofluorescence labeling and evaluated by confocal laser scanning microscopy. There was no detectable expression of BACE1 protein by activated Microglial cells of the ameboid or ramified phenotype in any of the lesion paradigms studied. In contrast, BACE1 expression by reactive astrocytes was evident in chronic but not in acute models of gliosis. Additionally, we observed BACE1-immunoreactive astrocytes in proximity to beta-amyloid plaques in the brains of aged Tg2576 mice and Alzheimer's disease patients.