Three-dimensional tomographic imaging and characterization of iron compounds within Alzheimer's plaque core material.
Three-dimensional tomographic imaging and characterization of iron compounds within Alzheimer's plaque core material.
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DOI：
10.3233/jad-2008-14211
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发表时间：
2008
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影响因子：
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通讯作者：
J. Collingwood;R. Chong;T. Kasama;L. Cervera-Gontard;R. Dunin‐Borkowski;George Perry;M. Pósfai;S. Siedlak;E. Simpson;Mark A. Smith;J. Dobson
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作者：
J. Collingwood;R. Chong;T. Kasama;L. Cervera-Gontard;R. Dunin‐Borkowski;George Perry;M. Pósfai;S. Siedlak;E. Simpson;Mark A. Smith;J. Dobson
尽管50多年来人们已经知道铁的异常浓度与几乎所有的神经退行性疾病（包括阿尔茨海默病）有关，但其起源、性质和作用仍然是一个谜。在这里，我们使用高分辨率透射电子显微镜（HR-TEM），能量色散X射线（EDX）光谱和电子能量损失光谱（EELS），电子断层扫描和电子衍射成像和表征富含铁的斑块核心材料-阿尔茨海默病病理学的标志-在三维空间。在这些核心中，我们明确地确定生物磁铁矿和/或磁赤铁矿为主要的铁化合物。我们的研究结果表明，异常铁生物矿化过程可能发生在斑块或周围病变组织，并可能在异常肽聚集中发挥作用。磁铁矿核心的大小分布意味着铁蛋白前体的形成，暗示了大脑中主要铁储存蛋白的功能障碍。
Although it has been known for over 50 years that abnormal concentrations of iron are associated with virtually all neurodegenerative diseases, including Alzheimer's disease, its origin, nature and role have remained a mystery. Here, we use high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray (EDX) spectroscopy and electron energy-loss spectroscopy (EELS), electron tomography, and electron diffraction to image and characterize iron-rich plaque core material - a hallmark of Alzheimer's disease pathology - in three dimensions. In these cores, we unequivocally identify biogenic magnetite and/or maghemite as the dominant iron compound. Our results provide an indication that abnormal iron biomineralization processes are likely occurring within the plaque or the surrounding diseased tissue and may play a role in aberrant peptide aggregation. The size distribution of the magnetite cores implies formation from a ferritin precursor, implicating a malfunction of the primary iron storage protein in the brain.