Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology.
Gender and genetic background effects on brain metal levels in APP transgenic and normal mice: implications for Alzheimer beta-amyloid pathology.
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DOI：
10.1016/j.jinorgbio.2006.02.010
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发表时间：
2006-05
影响因子：
3.9
通讯作者：
Christa J. Maynard;R. Cappai;I. Volitakis;R. Cherny;C. Masters;Qiao-Xin Li;A. Bush
中科院分区：
文献类型：
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作者：
Christa J. Maynard;R. Cappai;I. Volitakis;R. Cherny;C. Masters;Qiao-Xin Li;A. Bush
阿尔茨海默病（AD）的发病率在任何年龄的女性都高于男性，在几种AD转基因小鼠模型中淀粉样蛋白病理学的发展也是如此。由于金属参与AD发病机制，不同性别的金属代谢的差异可能有助于AD风险的性别差异。在这项研究中，我们研究了两种不同背景品系小鼠以及过表达人类淀粉样前体蛋白（APP）和淀粉样β蛋白（Aβ）的小鼠在整个寿命期间脑金属水平的性别差异。我们证明一贯较低的铜和较高的锰水平的女性相比，男性在任何年龄的研究。铜和锰水平的性别差异与APP/Aβ表达无关。AD脑表现出铜水平降低和锰水平升高，过表达APP或Aβ的转基因小鼠也是如此。与B6/DBA相比，B6/SJL背景的小鼠中Cu、Fe和Co水平的年龄依赖性升高被发现显著更大。如果铜消耗和/或锰水平升高导致AD发病机制，那么这些大脑金属水平的自然性别差异可能会导致女性患AD的倾向增加。
The incidence of Alzheimer’s disease (AD) is greater in women than men at any age, as is the development of amyloid pathology in several transgenic mouse models of AD. Due to the involvement of metals in AD pathogenesis, variations between the sexes in metal metabolism may contribute to the sex difference in AD risk. In this study, we investigated sex differences in brain metal levels across the lifespan in mice of two different background strains, as well as in mice overexpressing the human amyloid precursor protein (APP) and amyloid-β protein (Aβ). We demonstrate consistently lower Cu and higher Mn levels in females compared with males at any age studied. The sex differences in Cu and Mn levels are independent of APP/Aβ expression. AD brain exhibits decreased Cu and increased Mn levels, as do transgenic mice overexpressing APP or Aβ. The age-dependent elevations of Cu, Fe and Co levels were found to be significantly greater in mice of B6/SJL background compared with B6/DBA. If depleting Cu and/or rising Mn levels contribute to AD pathogenesis, natural sex differences in these brain metal levels may contribute to the increased propensity of females to develop AD.