Amyloid plaques in PSAPP mice bind less metal than plaques in human Alzheimer's disease.
Amyloid plaques in PSAPP mice bind less metal than plaques in human Alzheimer's disease.
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DOI：
10.1016/j.neuroimage.2009.05.063
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发表时间：
2009-10-01
期刊：
影响因子：
5.7
通讯作者：
Miller, Lisa M.
中科院分区：
文献类型：
--
作者：
Leskovjan, Andreana C.;Lanzirotti, Antonio;Miller, Lisa M.
关键词：
淀粉样β蛋白(Aβ)是阿尔茨海默病(AD)斑块的主要成分，是该病的关键病理特征。金属离子锌(锌)、铜(铜)、铁(铁)和钙(钙)在人类淀粉样斑块中升高，被认为与神经退行性变有关。转基因AD小鼠模型也显示出淀粉样斑块，但没有表现出人类观察到的高度神经变性。在这项研究中，我们使用同步辐射X射线荧光(XRF)微探针对代表终末期AD(N=6)的PSAPP转基因小鼠模型中的锌、铜、铁和钙离子的分布进行了成像。为了解释斑块密度的差异，用同步加速器傅里叶变换红外光谱(FTIRM)对相同样品的相对蛋白质含量进行了成像。FTIRM结果显示，与周围组织相比，斑块中的蛋白质含量增加了61%。在对蛋白质密度进行归一化后，我们发现PSAPP斑块中的锌含量只增加了29%，而且斑块中的铜、铁和钙实际上比周围组织少。由于与Aβ的金属结合被认为会诱导对神经元有毒的氧化还原化学，因此PSAPP小鼠的金属结合减少与这些动物没有神经退变是一致的。这些发现与在人类AD斑块中观察到的高金属离子含量形成了鲜明对比，进一步暗示了金属离子在人类AD病理中的作用。
Amyloid beta (Aβ) is the primary component of Alzheimer’s disease (AD) plaques, a key pathological feature of the disease. Metal ions of zinc (Zn), copper (Cu), iron (Fe), and calcium (Ca) are elevated in human amyloid plaques and are thought to be involved in neurodegeneration. Transgenic mouse models of AD also exhibit amyloid plaques, but fail to exhibit the high degree of neurodegeneration observed in humans. In this study, we imaged the Zn, Cu, Fe, and Ca ion distribution in the PSAPP transgenic mouse model representing end-stage AD (N = 6) using synchrotron X-ray fluorescence (XRF) microprobe. In order to account for differences in density in the plaques, the relative protein content was imaged with synchrotron Fourier transform infrared microspectroscopy (FTIRM) on the same samples. FTIRM results revealed a 61% increase in protein content in the plaques compared to the surrounding tissue. After normalizing to protein density, we found that the PSAPP plaques contained only a 29% increase in Zn and there was actually less Cu, Fe, and Ca in the plaque compared to the surrounding tissue. Since metal-binding to Aβ is thought to induce redox chemistry that is toxic to neurons, the reduced metal-binding in PSAPP mice is consistent with the lack of neurodegeneration in these animals. These findings were in stark contrast to the high metal ion content observed in human AD plaques, further implicating the role of metal ions in human AD pathology.
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