Microglial response to amyloid plaques in APPsw transgenic mice.
Microglial response to amyloid plaques in APPsw transgenic mice.
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发表时间：
1998
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通讯作者：
S. Frautschy;Fusheng Yang;Michael Irrizarry;B. Hyman;T. Saido;K. Hsiao;G. Cole
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作者：
S. Frautschy;Fusheng Yang;Michael Irrizarry;B. Hyman;T. Saido;K. Hsiao;G. Cole
小胶质细胞活化是阿尔茨海默病（AD）炎症反应的核心。最近描述的小鼠品系Tg（HuAPP 695.K670N/M671 L）2576表达具有家族性AD基因突变、年龄相关性淀粉样蛋白沉积和记忆缺陷的人淀粉样蛋白前体蛋白，发现其产生显著的小胶质细胞应答，使用Griffonia simplicifolia凝集素或磷酸酪氨酸探针鉴定小胶质细胞。Griffonia simplicifolia凝集素和磷酸酪氨酸染色均显示强烈标记的通常，增大的小胶质细胞聚集在斑块内和周围，这与β-淀粉样蛋白形成相关的小胶质细胞活化一致。使用冠状磷酸酪氨酸免疫染色切片的定量图像分析，转基因阳性的10至16个月大，半合子，杂交Tg 2576（APPsw）的动物表现出显着增加的小胶质细胞密度和大小的斑块形成区域的海马和额叶，内嗅，枕叶皮质。作为与斑块中心的距离的函数的小胶质细胞的定量分析（A β肽和小胶质细胞的双标记）揭示了与邻近区域相比斑块内的小胶质细胞数量和面积的高度显著的2 - 5倍升高。Tg 2576 β-淀粉样蛋白斑块形成小鼠应该是一个有用的系统，用于评估小胶质细胞介导的炎症反应的后果，β-淀粉样蛋白和开发抗炎治疗策略阿尔茨海默病。这些结果提供了第一个定量的联系β-淀粉样蛋白斑块形成和小胶质细胞激活的动物模型与神经炎斑块和记忆缺陷。
Microglial activation is central to the inflammatory response in Alzheimer's Disease (AD). A recently described mouse line, Tg(HuAPP695.K670N/M671L)2576, expressing human amyloid precursor protein with a familial AD gene mutation, age-related amyloid deposits, and memory deficits, was found to develop a significant microglial response using Griffonia simplicifolia lectin or phosphotyrosine probe to identify microglia Both Griffonia simplicifolia lectin and phosphotyrosine staining showed increased numbers of intensely labeled, often enlarged microglia clustered in and around plaques, consistent with microglial activation related to beta-amyloid formation. Using quantitative image analysis of coronal phosphotyrosine-immunostained sections, transgene-positive 10- to 16-month-old, hemizygous, hybrid Tg2576 (APPsw) animals showed significantly increased microglial density and size in plaque-forming areas of hippocampus and frontal, entorhinal, and occipital cortex. Quantitative analysis of microglia as a function of distance from the center of plaques (double labeled for A beta peptide and microglia) revealed highly significant, two- to fivefold elevations in microglial number and area within plaques compared with neighboring regions. Tg2576 beta-amyloid-plaque-forming mice should be a useful system for assessing the consequences of the microglial-mediated inflammatory response to beta-amyloid and developing anti-inflammatory therapeutic strategies for Alzheimer's disease. These results provide the first quantitative link between beta-amyloid plaque formation and microglial activation in an animal model with neuritic plaques and memory deficits.