Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease.
Age-dependent changes in brain, CSF, and plasma amyloid (beta) protein in the Tg2576 transgenic mouse model of Alzheimer's disease.
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发表时间：
2001
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通讯作者：
T. Kawarabayashi;L. Younkin;T. Saido;M. Shoji;K. Ashe;S. Younkin
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作者：
T. Kawarabayashi;L. Younkin;T. Saido;M. Shoji;K. Ashe;S. Younkin
通过ELISA、免疫印迹和免疫细胞化学评价淀粉样β蛋白（Abeta）在阿尔茨海默病（AD）Tg 2576小鼠模型中的积累。Abeta的变化开始于6-7个月，因为出现了需要甲酸溶解的SDS不溶性形式的Abeta 42和Abeta 40。从6到10个月，这些不溶性形式呈指数增长。随着不溶性Abeta的出现，SDS可溶性Abeta略有下降，表明它可能正在转化为不溶性形式。我们的数据表明，它是全长未修饰的Abeta，最初在Tg 2576脑中积累。抗SDS的Abeta寡聚体和大多数N端截短或修饰的Abeta种类仅在较老的Tg 2576小鼠中发育，其中它们的水平远低于人类AD脑中的水平。在6至10个月之间，当SDS不溶性Abeta 42和Abeta 40很容易在每只动物中检测到时，组织病理学是最小的，因为只能识别出分离的Abeta核心。到12个月时，弥漫性斑块明显。从12到23个月，弥漫性斑块、具有淀粉样蛋白核心的神经炎斑块以及生物化学提取的A β 42和A β 40增加到与AD脑中观察到的水平相似的水平。与脑中A β的显著沉积一致，CSF A β降低，血浆A β显著降低。如果在人血浆中发生类似的下降，则血浆Abeta的测量可能用作AD的发病前生物标志物。
The accumulation of amyloid beta protein (Abeta) in the Tg2576 mouse model of Alzheimer's disease (AD) was evaluated by ELISA, immunoblotting, and immunocytochemistry. Changes in Abeta begin at 6-7 months as SDS-insoluble forms of Abeta42 and Abeta40 that require formic acid for solubilization appear. From 6 to 10 months, these insoluble forms increase exponentially. As insoluble Abeta appears, SDS-soluble Abeta decreases slightly, suggesting that it may be converting to an insoluble form. Our data indicate that it is full-length unmodified Abeta that accumulates initially in Tg2576 brain. SDS-resistant Abeta oligomers and most Abeta species that are N-terminally truncated or modified develop only in older Tg2576 mice, in which they are present at levels far lower than in human AD brain. Between 6 and 10 months, when SDS-insoluble Abeta42 and Abeta40 are easily detected in every animal, histopathology is minimal because only isolated Abeta cores can be identified. By 12 months, diffuse plaques are evident. From 12 to 23 months, diffuse plaques, neuritic plaques with amyloid cores, and biochemically extracted Abeta42 and Abeta40 increase to levels like those observed in AD brains. Coincident with the marked deposition of Abeta in brain, there is a decrease in CSF Abeta and a substantial, highly significant decrease in plasma Abeta. If a similar decline occurs in human plasma, it is possible that measurement of plasma Abeta may be useful as a premorbid biomarker for AD.