R Cardoso Bárbara, Hare Dominic J, Lind Monica, McLean Catriona A, Volitakis Irene, Laws Simon M, Masters Colin L, Bush Ashley I, Roberts Blaine R
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, Victoria 3052, Australia.
Faculty of Pharmaceutical Sciences, Department of Food and Experimental Nutrition, University of São Paulo , São Paulo 05508-000, Brazil.
ACS Chem Neurosci. 2017 Jul 19;8(7):1459-1464. doi: 10.1021/acschemneuro.7b00014. Epub 2017 May 3.
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 ε4 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 ε4 and selenium delivery into brain, and show changes in cellular selenium distribution in the Alzheimer's disease brain.
硒的抗氧化活性主要通过其掺入特定的硒蛋白来实现，有人提出这可能是一种减轻阿尔茨海默病神经元损失的神经保护方法。然而，关于阿尔茨海默病大脑中硒水平的信息并不一致。我们检测了阿尔茨海默病患者和对照脑组织颞叶皮质中硒的浓度和细胞分布。我们发现，阿尔茨海默病与脑匀浆可溶性（即胞质）和不溶性（即斑块和缠结）部分中硒浓度降低有关。APOE ε4等位基因的存在与颞叶皮质中总硒水平较低以及可溶性硒浓度较高相关。此外，我们发现年龄显著导致外周膜结合和囊泡部分中硒浓度降低。我们的研究结果表明APOE ε4与硒向大脑输送之间存在相关相互作用，并显示了阿尔茨海默病大脑中细胞硒分布的变化。
