Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation
Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation
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DOI：
10.1038/nm1123
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发表时间：
2004-11-01
期刊：
影响因子：
82.9
通讯作者：
Mucke, L
中科院分区：
文献类型：
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作者：
Cheng, IH;Palop, JJ;Mucke, L
淀粉样蛋白 (A) 肽内的北极突变会导致阿尔茨海默病。在体外，北极突变体 A 比野生型 A 更有效地形成（原）原纤维。我们培育了表达北极突变体人类淀粉样前体蛋白 (hAPP) 的转基因小鼠品系。尽管北极小鼠的 Abeta(1-42/1-40) 比率较低，但与表达野生型 A 的 hAPP 小鼠相比，北极小鼠的淀粉样蛋白斑形成速度更快且范围更广。因此，北极突变在体内具有高度淀粉样蛋白生成性。
The Arctic mutation within the amyloid-(A) peptide causes Alzheimer disease. In vitro, Arctic-mutant A forms (proto) fibrils more effectively than wild-type A. We generated transgenic mouse lines expressing Arctic-mutant human amyloid precursor proteins (hAPP). Amyloid plaques formed faster and were more extensive in Arctic mice than in hAPP mice expressing wild-type A, even though Arctic mice had lower Abeta(1-42/1-40) ratios. Thus, the Arctic mutation is highly amyloidogenic in vivo.