Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease.
Alpha-1-antichymotrypsin promotes beta-sheet amyloid plaque deposition in a transgenic mouse model of Alzheimer's disease.
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发表时间：
2001
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通讯作者：
L. Nilsson;K. Bales;G. Dicarlo;M. Gordon;D. Morgan;S. Paul;H. Potter
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作者：
L. Nilsson;K. Bales;G. Dicarlo;M. Gordon;D. Morgan;S. Paul;H. Potter
α（1）-抗胰凝乳蛋白酶（ACT）是一种急性期炎症蛋白，是阿尔茨海默病（AD）中淀粉样蛋白沉积物的组成部分，并已显示在体外催化淀粉样蛋白β-肽聚合。我们通过产生表达GFAP-ACT的转基因小鼠并将其与PDGF-hAPP/V717 F小鼠杂交，研究了ACT对体内淀粉样蛋白沉积的影响，PDGF-hAPP/V717 F小鼠以年龄依赖性的方式存款淀粉样蛋白。通过刚果红双折射测量的淀粉样沉积物的数量在双ACT/淀粉样前体蛋白（APP）转基因小鼠中比仅表达APP的转基因小鼠中增加，特别是在ACT表达最高的海马中，并且在早期增加之前总淀粉样β肽水平升高。我们的数据表明，ACT促进淀粉样蛋白沉积，并提供了一个特定的机制，炎症和随后的上调星形胶质细胞ACT表达在AD脑有助于AD的发病机制。
Alpha(1)-antichymotrypsin (ACT), an acute-phase inflammatory protein, is an integral component of the amyloid deposits in Alzheimer's disease (AD) and has been shown to catalyze amyloid beta-peptide polymerization in vitro. We have investigated the impact of ACT on amyloid deposition in vivo by generating transgenic GFAP-ACT-expressing mice and crossing them with the PDGF-hAPP/V717F mice, which deposit amyloid in an age-dependent manner. The number of amyloid deposits measured by Congo Red birefringence was increased in the double ACT/amyloid precursor protein (APP) transgenic mice compared with transgenic mice that only expressed APP, particularly in the hippocampus where ACT expression was highest, and the increase was preceded by elevated total amyloid beta-peptide levels at an early age. Our data demonstrate that ACT promotes amyloid deposition and provide a specific mechanism by which inflammation and the subsequent upregulation of astrocytic ACT expression in AD brain contributes to AD pathogenesis.