Bourassa Megan W, Leskovjan Andreana C, Tappero Ryan V, Farquhar Erik R, Colton Carol A, Van Nostrand William E, Miller Lisa M
Department of Chemistry, Stony Brook University, Stony Brook NY, USA.
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, USA.
Biomed Spectrosc Imaging. 2013 Apr 1;2(2):129-139. doi: 10.3233/BSI-130041.
In Alzheimer's disease (AD), alterations in metal homeostasis, including the accumulation of metal ions in the plaques and an increase of iron in the cortex, have been well documented but the mechanisms involved are poorly understood.
In this study, we compared the metal content in the plaques and the iron speciation in the cortex of three mouse models, two of which show neurodegeneration (5xFAD and Tg-SwDI/NOS2 (CVN) and one that shows very little neurodegeneration (PSAPP).
The Fe, Cu, and Zn contents and speciation were determined using synchrotron X-ray fluorescence microscopy (XFM) and X-ray absorption spectroscopy (XAS), respectively.
In the mouse models with reported significant neurodegeneration, we found that plaques contained ~25% more copper compared to the PSAPP mice. The iron content in the cortex increased at the late stage of the disease in all mouse models, but iron speciation remains unchanged.
The elevation of copper in the plaques and iron in the cortex is associated with AD severity, suggesting that these redox-active metal ions may be inducing oxidative damage and directly influencing neurodegeneration.
在阿尔茨海默病（AD）中，金属稳态的改变，包括金属离子在斑块中的积累以及皮质中铁含量的增加，已有充分记录，但其中涉及的机制尚不清楚。
在本研究中，我们比较了三种小鼠模型斑块中的金属含量以及皮质中的铁形态，其中两种模型表现出神经退行性变（5xFAD和Tg-SwDI/NOS2（CVN）），另一种几乎没有神经退行性变（PSAPP）。
分别使用同步加速器X射线荧光显微镜（XFM）和X射线吸收光谱（XAS）测定铁、铜和锌的含量及形态。
在报告有明显神经退行性变的小鼠模型中，我们发现与PSAPP小鼠相比，斑块中的铜含量高出约25%。在所有小鼠模型中，疾病晚期皮质中的铁含量增加，但铁形态保持不变。
斑块中铜含量的升高以及皮质中铁含量的增加与AD的严重程度相关，表明这些具有氧化还原活性的金属离子可能会诱导氧化损伤并直接影响神经退行性变。
