Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.
Iron Biochemistry is Correlated with Amyloid Plaque Morphology in an Established Mouse Model of Alzheimer's Disease.
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DOI：
10.1016/j.chembiol.2017.07.014
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发表时间：
2017-10
影响因子：
8.6
通讯作者：
N. Telling;James Everett;J. Collingwood;J. Dobson;G. van der Laan;Joseph J. Gallagher;Jian Wang
中科院分区：
文献类型：
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作者：
N. Telling;James Everett;J. Collingwood;J. Dobson;G. van der Laan;Joseph J. Gallagher;Jian Wang
阿尔茨海默病 (AD) 的一个标志性特征是大脑中β-淀粉样蛋白 (Aβ) 原纤维的聚集。然而，Aβ 与 AD 病理学之间的联系仍不完全清楚。有人提出，Aβ1-42 肽聚集引起的神经毒性部分可以通过金属离子结合相互作用来解释。我们使用亚微米分辨率的先进 X 射线显微镜技术，从已建立的过度产生 Aβ 的小鼠模型中研究了完整皮质中铁生物化学与 AD 病理学之间的关系。我们发现淀粉样斑块形态与铁直接相关，以及铁-淀粉样蛋白复合物形成的证据。我们还表明，皮质组织中的铁生物矿物沉积物含有矿物磁铁矿，并提供了 Aβ 诱导的铁化学还原可能在体内发生的证据。我们的观察指出了铁在淀粉样蛋白沉积和 AD 病理学中的特定作用，并可能影响 AD 铁修饰疗法的开发。
A signature characteristic of Alzheimer's disease (AD) is aggregation of amyloid-beta (Aβ) fibrils in the brain. Nevertheless, the links between Aβ and AD pathology remain incompletely understood. It has been proposed that neurotoxicity arising from aggregation of the Aβ1-42peptide can in part be explained by metal ion binding interactions. Using advanced X-ray microscopy techniques at sub-micron resolution, we investigated relationships between iron biochemistry and AD pathology in intact cortex from an established mouse model over-producing Aβ. We found a direct correlation of amyloid plaque morphology with iron, and evidence for the formation of an iron-amyloid complex. We also show that iron biomineral deposits in the cortical tissue contain the mineral magnetite, and provide evidence that Aβ-induced chemical reduction of iron could occurin vivo. Our observations point to the specific role of iron in amyloid deposition and AD pathology, and may impact development of iron-modifying therapeutics for AD.