Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease
Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease
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DOI：
10.1016/j.neuron.2006.01.022
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发表时间：
2006-02-16
期刊：
影响因子：
16.2
通讯作者：
Rivest, S
中科院分区：
文献类型：
--
作者：
Simard, AR;Soulet, D;Rivest, S
小胶质细胞是大脑的免疫细胞。在这里，我们显示了一个巨大的渗透高度分歧和细长的小胶质细胞的核心淀粉样蛋白斑块在转基因小鼠模型阿尔茨海默氏病（AD）。这些细胞中的许多来源于骨髓，β-淀粉样蛋白-40和-42亚型能够触发这种化学吸引。这些新募集的细胞还表现出对大脑中外源性和内源性β-淀粉样蛋白的特异性免疫反应。创建一个新的AD转基因小鼠，表达的胸苷激酶蛋白的控制下的CD 11b启动子，使我们能够表明，血液来源的小胶质细胞，而不是他们的居民同行有能力消除淀粉样蛋白沉积的细胞特异性吞噬机制。因此，这些骨髓来源的小胶质细胞在限制淀粉样蛋白沉积方面非常有效。旨在改善其招募的治疗策略可能会成为消除毒性老年斑的新的强大工具。
Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the beta-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune reaction to both exogenous and enclogenous beta-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed us to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia are thus very efficient in restricting amyloid deposits. Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques.