Iron, copper, and iron regulatory protein 2 in Alzheimer's disease and related dementias
Iron, copper, and iron regulatory protein 2 in Alzheimer's disease and related dementias
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DOI：
10.1016/j.neulet.2007.02.077
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发表时间：
2007-05-11
影响因子：
2.5
通讯作者：
Kirsch, Wolff M.
中科院分区：
文献类型：
--
作者：
Magaki, Shino;Raghavan, Ravi;Kirsch, Wolff M.
越来越多的证据表明铁和铜代谢的改变在神经退行性疾病如阿尔茨海默病（AD）的发病机制中起作用。然而，各种形式的铁在AD的不同阶段的水平的不平衡还没有被检查。在这项初步研究中，我们提取和测量轻中度AD（n = 3），重度AD（n = 8）和路易体痴呆（DLB，n = 6）患者的额叶皮层和海马中的松散结合，非血红素和总铁和铜的水平，使用石墨炉原子吸收光谱法（GFAAS）。此外，通过免疫组织化学方法检查了铁调节蛋白2（IRP 2）的表达与AD和DLB、淀粉样斑块、神经原纤维缠结（NFT）和路易体的病理标志的关系。我们发现轻中度和重度AD患者海马白色物质中松散结合铁显著减少，重度AD患者海马灰质中非血红素铁有增加的趋势。此外，与对照组相比，在重度AD和DLB额叶皮质中观察到总铜水平降低，表明AD和DLB的脑金属水平不平衡。轻中度AD患者中松散结合铁的减少可能与AD开始阶段的髓鞘破坏有关，并暗示铁失调是AD发病机制的早期事件。(c)2007年由Elsevier爱尔兰有限公司出版。
Accumulating evidence implicates a role for altered iron and copper metabolism in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, imbalances in the levels of the various forms of iron at different stages of AD have not been examined. In this pilot study we extracted and measured the levels of loosely bound, non-heme and total iron and copper in the frontal cortex and hippocampus of patients with mild-moderate AD (n = 3), severe AD (n = 8) and dementia with Lewy bodies (DLB, n = 6), using graphite furnace atomic absorption spectrometry (GFAAS). Additionally, the expression of iron regulatory protein 2 (IRP2) was examined in relation to the pathological hallmarks of AD and DLB, amyloid plaques, neurofibrillary tangles (NFT), and Lewy bodies, by immunohistochemistry. We found significantly decreased loosely bound iron in the hippocampal white matter of mild-moderate and severe AD patients and a trend towards increased non-heme iron in the hippocampal gray matter of severe AD patients. Furthermore, decreased levels of total copper were seen in severe AD and DLB frontal cortex compared to controls, suggesting an imbalance in brain metal levels in both AD and DLB. The decrease in loosely bound iron in mild-moderate AD patients may be associated with myelin breakdown seen in the beginning stages of AD and implicates that iron dysregulation is an early event in AD pathogenesis. (c) 2007 Published by Elsevier Ireland Ltd.