The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease
The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease
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DOI：
10.1021/acschemneuro.7b00014
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发表时间：
2017-07-01
影响因子：
5
通讯作者：
Roberts, Blaine R.
中科院分区：
文献类型：
--
作者：
Cardoso, Barbara R.;Hare, Dominic J.;Roberts, Blaine R.
硒的抗氧化活性主要是通过掺入专用的硒蛋白而赋予的，已被认为是一种可能的神经保护方法，用于减轻阿尔茨海默病中的神经元损失。然而，有关阿尔茨海默病大脑中硒水平的信息不一致。我们检查了阿尔茨海默病和对照脑组织颞叶皮层中硒的浓度和细胞区室化。我们发现阿尔茨海默氏病与脑匀浆的可溶性（即胞质）和不溶性（即斑块和缠结）部分中的硒浓度降低有关。 APOE epsilon 4 等位基因的存在与颞叶皮层中较低的总硒水平和较高的可溶性硒浓度相关。此外，我们发现年龄显着导致外周膜结合部分和囊泡部分中的硒浓度降低。我们的研究结果表明 APOE epsilon 4 和硒进入大脑之间存在相关的相互作用，并显示了阿尔茨海默病大脑中细胞硒分布的变化。
The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer's disease brain. We examined the concentration and cellular compartmentalization of selenium in the temporal cortex of Alzheimer's disease and control brain tissue. We found that Alzheimer's disease was associated with decreased selenium concentration in both soluble (i.e., cytosolic) and insoluble (i.e., plaques and tangles) fractions of brain homogenates. The presence of the APOE epsilon 4 allele correlated with lower total selenium levels in the temporal cortex and a higher concentration of soluble selenium. Additionally, we found that age significantly contributed to lower selenium concentrations in the peripheral membrane-bound and vesicular fractions. Our findings suggest a relevant interaction between APOE epsilon 4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimer's disease brain.