Modest Amyloid Deposition is Associated with Iron Dysregulation, Microglial Activation, and Oxidative Stress
Modest Amyloid Deposition is Associated with Iron Dysregulation, Microglial Activation, and Oxidative Stress
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DOI：
10.3233/jad-2011-110614
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Lynch, Marina A.
中科院分区：
文献类型：
--
作者：
Gallagher, Joseph J.;Finnegan, Mary E.;Lynch, Marina A.
有一个公认的文献表明铁在脑组织和阿尔茨海默病（AD）之间的关系。最近，已经清楚的是，AD与可能由小胶质细胞活化引起的神经炎症和氧化变化相关。在这项研究中，我们研究了相关的变化，小胶质细胞的激活，氧化应激，铁失调的小鼠模型的AD表现出早期淀粉样蛋白沉积。对A β PP/PS1转基因小鼠制备的完整脑组织切片进行微焦点X射线吸收光谱分析，发现存在磁铁矿（一种混合价氧化铁），以及与含淀粉样蛋白β斑块相关的组织中铁水平局部升高。证据表明，小胶质细胞活化标志物CD 11b和CD 68以及星形胶质细胞活化标志物GFAP的表达增加，并且组织化学确定为与含淀粉样蛋白β的斑块相邻。这些研究结果支持的论点，除了神经胶质细胞活化和氧化应激，铁失调是AD病理学的早期事件。
There is a well-established literature indicating a relationship between iron in brain tissue and Alzheimer's disease (AD). More recently, it has become clear that AD is associated with neuroinflammatory and oxidative changes which probably result from microglial activation. In this study, we investigated the correlative changes in microglial activation, oxidative stress, and iron dysregulation in a mouse model of AD which exhibits early-stage amyloid deposition. Microfocus X-ray absorption spectroscopy analysis of intact brain tissue sections prepared from A beta PP/PS1 transgenic mice revealed the presence of magnetite, a mixed-valence iron oxide, and local elevations in iron levels in tissue associated with amyloid-beta-containing plaques. The evidence indicates that the expression of markers of microglial activation, CD11b and CD68, and astrocytic activation, GFAP, were increased, and were histochemically determined to be adjacent to amyloid-beta-containing plaques. These findings support the contention that, in addition to glial activation and oxidative stress, iron dysregulation is an early event in AD pathology.