Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation
Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation
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DOI：
10.1038/8438
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发表时间：
1999-05-01
期刊：
影响因子：
82.9
通讯作者：
Tabira, T
中科院分区：
文献类型：
--
作者：
Chui, DH;Tanahashi, H;Tabira, T
早老素1（PS-1）的家族性阿尔茨海默病突变增强A β 1-42的产生，表明PS-1参与淀粉样蛋白生成。然而，PS-1转基因小鼠未能在其脑中显示淀粉样蛋白斑块。由于PS-1突变在体外促进了神经元凋亡，我们在PS-1转基因小鼠中进行了仔细的定量研究，发现在年龄大于13个月的具有家族性阿尔茨海默病突变体PS-1的小鼠（老年小鼠）中，神经变性显著加速，而没有淀粉样蛋白斑块形成。然而，有显着更多的神经元含有细胞内沉积的A β 42在老年突变转基因小鼠。我们的数据表明PS-1突变的致病作用是淀粉样级联反应的上游。
Familial Alzheimer disease mutations of presenilin 1 (PS-1) enhance the generation of A beta 1-42, indicating that PS-1 is involved in amyloidogenesis. However, PS-l transgenic mice have failed to show amyloid plaques in their brains. Because PS-l mutations facilitate apoptotic neuronal death in vitro, we did careful quantitative studies in PS-1 transgenic mice and found that neurodegeneration was significantly accelerated in mice older than 13 months (aged mice) with familial Alzheimer disease mutant PS-1, without amyloid plaque formation. However, there were significantly more neurons containing intracellularly deposited A beta 42 in aged mutant transgenic mice. Our data indicate that the pathogenic role of the PS-1 mutation is upstream of the amyloid cascade.