A specific amyloid-beta protein assembly in the brain impairs memory.
A specific amyloid-beta protein assembly in the brain impairs memory.
复制标题
DOI：
--
复制
发表时间：
2006
期刊：
影响因子：
64.8
通讯作者：
S. Lesné;M. T. Koh;L. Kotilinek;R. Kayed;C. Glabe;A. Yang;M. Gallagher;K. Ashe
中科院分区：
文献类型：
--
作者：
S. Lesné;M. T. Koh;L. Kotilinek;R. Kayed;C. Glabe;A. Yang;M. Gallagher;K. Ashe
记忆功能通常随着年龄的增长而下降，并且被认为最初是由于突触功能的变化而不是神经元的损失而恶化。有些人然后继续发展阿尔茨海默病与神经变性。在这里，我们使用Tg 2576小鼠，表达与阿尔茨海默病相关的人类淀粉样β前体蛋白（APP）变体，以研究在没有神经变性或淀粉样β蛋白淀粉样变性的情况下记忆力下降的原因。年轻的Tg 2576小鼠（14个月大）形成了大量含有β淀粉样蛋白的神经炎斑块（参考文献3-6）。我们发现中年Tg 2576小鼠的记忆缺陷是由56 kDa可溶性淀粉样蛋白-β组装体的细胞外积累引起的，我们称之为Abeta*56（Abeta星星56）。从受损的Tg 2576小鼠大脑中纯化的Abeta*56在给予幼鼠时会扰乱记忆。我们认为Abeta*56损害记忆独立于斑块或神经元损失，并可能导致与阿尔茨海默病相关的认知缺陷。
Memory function often declines with age, and is believed to deteriorate initially because of changes in synaptic function rather than loss of neurons. Some individuals then go on to develop Alzheimer's disease with neurodegeneration. Here we use Tg2576 mice, which express a human amyloid-beta precursor protein (APP) variant linked to Alzheimer's disease, to investigate the cause of memory decline in the absence of neurodegeneration or amyloid-beta protein amyloidosis. Young Tg2576 mice ( 14 months old) form abundant neuritic plaques containing amyloid-beta (refs 3-6). We found that memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta assembly, which we term Abeta*56 (Abeta star 56). Abeta*56 purified from the brains of impaired Tg2576 mice disrupts memory when administered to young rats. We propose that Abeta*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.