Amyloid cored plaques in Tg2576 transgenic mice are characterized by giant plaques, slightly activated microglia, and the lack of paired helical filament-typed, dystrophic neurites
Amyloid cored plaques in Tg2576 transgenic mice are characterized by giant plaques, slightly activated microglia, and the lack of paired helical filament-typed, dystrophic neurites
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DOI：
10.1007/s00428-002-0643-8
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发表时间：
2002-10-01
期刊：
影响因子：
3.5
通讯作者：
Nakazato, Y
中科院分区：
文献类型：
--
作者：
Sasaki, A;Shoji, M;Nakazato, Y
采用免疫组织化学和电镜技术对携带瑞典突变和阿尔茨海默病（AD）的人淀粉样蛋白前体蛋白Tg2576转基因小鼠的大脑进行了检测，以阐明转基因小鼠淀粉样蛋白相关病理特征。在12至29个月大的Tg2576小鼠中，新皮层和海马中的嗜血性核心斑块被所有Abeta1-， Abeta40-和42特异性抗体标记，与AD的经典斑块中所见相同。然而，在年龄较大的小鼠（18-29个月）中，大尺寸（核心直径为> - 50 μ m）斑块比在AD患者中更常见（约占总核心斑块的20% vs 2%）， Tg2576小鼠含有巨大的斑块（核心直径为> - 75 μ m），而在AD患者的大脑中几乎从未见过。在银浸渍的转基因小鼠的核斑块中，既没有观察到线状结构，也没有观察到周围冠状结构。免疫组织化学结果显示，斑块伴发小胶质细胞细胞质轻微增大，具有一致的Mac-1和macrosialin（小鼠CD68）标记，以及la抗原和巨噬细胞集落刺激因子受体的部分标记。超微结构上，在大的、有核的斑块中，细胞外淀粉样原纤维周围的小胶质细胞显示一些具有吞噬活性的细胞器，如次级溶酶体、致密体，但细胞内淀粉样原纤维不明显。转基因小鼠斑块中的营养不良神经突含有许多致密的多层小体，但没有成对的螺旋细丝。我们的研究结果表明，在Tg2576小鼠中，没有冠状体或成对螺旋细丝型、营养不良的神经突的巨大核心斑块是典型特征，并且转基因小鼠中斑块相关的小胶质细胞被激活，具有吞噬功能，但不足以消化细胞外沉积的淀粉样原纤维。
We examined the brains of Tg2576 transgenic mice carrying human amyloid precursor protein with the Swedish mutation and Alzheimer's disease (AD) by means of immunohistochemistry and electron microscopy to clarify the characteristics of amyloid-associated pathology in the transgenic mice. In 12- to 29-month-old Tg2576 mice, congophilic cored plaques in the neocortex and hippocampus were labeled by all of the Abeta1-, Abeta40- and 42-specific antibodies, as seen in the classical plaques in AD. However, large-sized (>50 mum in core diameter) plaques were seen more frequently in the older mice (18-29 months) than in those with AD (approximately 20% vs 2% in total cored plaques), and Tg2576 mice contained giant plaques (>75 mum in core diameter), which were almost never seen in the brain of those with AD. Neither thread-like structures nor peripheral coronas were observed in the cored plaques of the transgenic mice in the silver impregnations. Immunohistochemically, plaque-accompanied microglia showed a slight enlargement of the cytoplasm with consistent labeling of Mac-1 and macrosialin (murine CD68), and with partial labeling of la antigen and macrophage-colony stimulating factor receptor. Ultrastructurally, the microglia surrounding the extracellular amyloid fibrils in the large, cored plaques showed some organella with phagocytic activity, such as secondary lysosomal, dense bodies, but intracellular amyloid fibrils were not evident. Dystrophic neurites in the plaques of the transgenic mice contained many dense multilaminar bodies, but no paired helical filaments. Our results suggest that giant cored plaques without coronas or paired helical filament-typed, dystrophic neurites are characteristic in Tg2576 mice, and that plaque-associated microglia in transgenic mice are activated to be in phagocytic function but not sufficient enough to digest extracellularly deposited amyloid fibrils.