Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease.
Increased brain iron coincides with early plaque formation in a mouse model of Alzheimer's disease.
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DOI：
10.1016/j.neuroimage.2010.11.073
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发表时间：
2011-03-01
期刊：
影响因子：
5.7
通讯作者：
Miller LM
中科院分区：
文献类型：
--
作者：
Leskovjan AC;Kretlow A;Lanzirotti A;Barrea R;Vogt S;Miller LM
在晚期人类阿尔茨海默病中观察到的脑铁含量升高是早期诊断的潜在目标。然而，铁积累的时间过程目前尚不清楚。使用淀粉样斑块形成的PSAPP小鼠模型，我们使用X射线荧光显微镜（XFM）对皮质和海马中的金属离子含量和分布[铁（Fe）、铜（Cu）和锌（Zn）]进行了时间过程研究。我们发现，在早期阶段，皮质中的铁比年龄匹配的对照组高34%，对应于斑块形成的开始。铁的升高与淀粉样斑块无关。有趣的是，直到最近的时间点（56周），淀粉样蛋白斑块中的金属离子都没有升高，其中只有Zn含量显著升高了38%。由于人类阿尔茨海默病的神经病理学变化被认为在第一次认知症状出现前几年就发生了，因此脑铁含量的定量可能是阿尔茨海默病早期诊断的有力标志。
Elevated brain iron content, which has been observed in late stage human Alzheimer’s disease, is a potential target for early diagnosis. However, the time course for iron accumulation is currently unclear. Using the PSAPP mouse model of amyloid plaque formation, we conducted a time course study of metal ion content and distribution [iron (Fe), copper (Cu), and zinc (Zn)] in the cortex and hippocampus using X-ray fluorescence microscopy (XFM). We found that iron in the cortex was 34% higher than age-matched controls at an early stage, corresponding to the commencement of plaque formation. The elevated iron was not associated with the amyloid plaques. Interestingly, none of the metal ions were elevated in the amyloid plaques until the latest time point (56 weeks), where only the Zn content was significantly elevated by 38%. Since neuropathological changes in human Alzheimer’s disease are presumed to occur years before the first cognitive symptoms appear, quantification of brain iron content could be a powerful marker for early diagnosis of Alzheimer’s disease.
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