Yumoto Institute of Neurology, Kawadacho 6-11, Shinjuku-ku, Tokyo 162-0054, Japan.
J Inorg Biochem. 2009 Nov;103(11):1579-84. doi: 10.1016/j.jinorgbio.2009.07.023. Epub 2009 Aug 15.
Aluminum (Al) exposure has been reported to be a risk factor for Alzheimer's disease (senile dementia of Alzheimer type), although the role of Al in the etiology of Alzheimer's disease remains controversial. We examined the presence of Al in the Alzheimer's brain using energy-dispersive X-ray spectroscopy combined with transmission electron microscopy (TEM-EDX). TEM-EDX analysis allows simultaneous imaging of subcellular structures with high spatial resolution and analysis of small quantities of elements contained in the same subcellular structures. We identified senile plaques by observation using TEM and detected Al in amyloid fibers in the cores of senile plaques located in the hippocampus and the temporal lobe by EDX. Phosphorus and calcium were also present in the amyloid fibers. No Al could be detected in the extracellular space in senile plaques or in the cytoplasm of nerve cells. In this study, we demonstrated colocalization of Al and beta-amyloid (Abeta) peptides in amyloid fibers in the cores of senile plaques. The results support the following possibilities in the brains of patients with Alzheimer's disease: Al could be involved in the aggregation of Abeta peptides to form toxic fibrils; Al might induce Abeta peptides into the beta-sheet structure; and Al might facilitate iron-mediated oxidative reactions, which cause severe damage to brain tissues.
铝（Al）暴露已被报道为阿尔茨海默病（老年痴呆症）的危险因素，尽管铝在阿尔茨海默病发病机制中的作用仍存在争议。我们使用能量色散 X 射线光谱学结合透射电子显微镜（TEM-EDX）检查了阿尔茨海默病大脑中的铝。TEM-EDX 分析允许对亚细胞结构进行高空间分辨率的同时成像，并对同一亚细胞结构中包含的少量元素进行分析。我们通过 TEM 观察来鉴定老年斑，并通过 EDX 检测到位于海马体和颞叶的老年斑核心中的淀粉样纤维中的铝。磷和钙也存在于淀粉样纤维中。在老年斑的细胞外空间或神经细胞的细胞质中均无法检测到铝。在这项研究中，我们证明了老年斑核心中的淀粉样纤维中铝和β-淀粉样肽（Abeta）的共定位。这些结果支持阿尔茨海默病患者大脑中存在以下可能性：铝可能参与 Abeta 肽的聚集形成毒性纤维；铝可能诱导 Abeta 肽形成β-折叠结构；铝可能促进铁介导的氧化反应，从而对脑组织造成严重损伤。
