Department of Neuroscience, AFaR, Fatebenefratelli Hospital, Rome, Italy.
Front Biosci (Landmark Ed). 2012 Jan 1;17(2):451-72. doi: 10.2741/3938.
Many results from in vitro and animal studies have highlighted the important role played by specific metals, such as copper, iron and zinc, in the diverse toxic pathways on which Alzheimer's disease (AD) develops. Metals seem to mediate the aggregation and neurotoxicity of amyloid-beta (ABeta), the main constituent of the amyloid plaques, commonly seen in AD (1). The link between metals and AD has been mostly investigated with a focus on their local accumulation in defined areas of the brain critical for AD. In the present review, I have instead approached the issue from the different perspective of a systemic, rather than local, alteration of copper and iron status. This view is supported by the results of a series of in vivo studies demonstrating that abnormalities of metals homeostasis correlate with the main deficits and specific markers of AD, such as ABeta and Tau proteins in the cerebrospinal fluid. These findings clearly suggest that local metals accumulation in brain areas critical for AD should be viewed within a wider framework of metals systemic alteration.
许多体外和动物研究的结果强调了特定金属（如铜、铁和锌）在阿尔茨海默病（AD）发展的多种毒性途径中所起的重要作用。金属似乎介导了淀粉样蛋白-β（ABeta）的聚集和神经毒性，ABeta 是 AD 中常见的淀粉样斑块的主要成分（1）。金属与 AD 之间的联系主要是通过研究它们在大脑中对 AD 至关重要的特定区域的局部积累来进行的。在本综述中，我则从系统而不是局部改变铜和铁状态的不同角度来探讨这个问题。这一观点得到了一系列体内研究结果的支持，这些研究表明，金属动态平衡的异常与 AD 的主要缺陷和特定标志物（如脑脊液中的 ABeta 和 Tau 蛋白）相关。这些发现清楚地表明，应在更广泛的金属系统改变框架内看待大脑中与 AD 关键区域的局部金属积累。
