Wang Zi-Xuan, Tan Lan, Wang Hui-Fu, Ma Jing, Liu Jinyuan, Tan Meng-Shan, Sun Jia-Hao, Zhu Xi-Chen, Jiang Teng, Yu Jin-Tai
Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong Province, China.
Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
J Alzheimers Dis. 2015;47(3):565-81. doi: 10.3233/JAD-143108.
To evaluate whether iron, zinc, and copper levels in serum are disarranged in Alzheimer's disease (AD), we performed meta-analyses of all studies on the topic published from 1984 to 2014 and contextually carried out a replication study in serum as well. Our meta-analysis results showed that serum zinc was significantly lower in AD patients. Our replication and meta-analysis results showed that serum copper was significantly higher in AD patients than in healthy controls, so our findings were consistent with the conclusions of four previously published copper meta-analyses. Even if a possible role of iron in the pathophysiology of the disease could not be ruled out, the results of our meta-analysis showed no change of serum iron levels in AD patients, but this conclusion was not robust and requires further investigation. The meta-regression analyses revealed that in some studies, differences in serum iron levels could be due to the different mean ages, while differences in zinc levels appeared to be due to the different sex ratios. However, the effect of sex ratio on serum zinc levels in our meta-analysis is subtle and needs further confirmation. Also, diverse demographic terms and methodological approaches appeared not to explain the high heterogeneity of our copper meta-analysis. Therefore, when investigating trace elements, covariants such as age and sex have to be taken into account in the analyses. In the light of these findings, we suggest that the possible alteration of serum zinc and copper levels are involved in the pathogenesis of AD.
为评估阿尔茨海默病（AD）患者血清中铁、锌和铜水平是否紊乱，我们对1984年至2014年发表的关于该主题的所有研究进行了荟萃分析，并在此背景下开展了血清重复研究。我们的荟萃分析结果显示，AD患者血清锌水平显著降低。我们的重复研究和荟萃分析结果显示，AD患者血清铜水平显著高于健康对照，因此我们的研究结果与之前发表的四项铜荟萃分析结论一致。即使不能排除铁在该疾病病理生理学中的可能作用，但我们的荟萃分析结果显示AD患者血清铁水平无变化，不过这一结论并不稳健，需要进一步研究。荟萃回归分析显示，在一些研究中，血清铁水平的差异可能归因于平均年龄不同，而锌水平的差异似乎归因于性别比例不同。然而，在我们的荟萃分析中，性别比例对血清锌水平的影响较为微妙，需要进一步证实。此外，不同的人口统计学指标和方法学途径似乎无法解释我们铜荟萃分析中的高异质性。因此，在研究微量元素时，分析中必须考虑年龄和性别等协变量。鉴于这些发现，我们认为血清锌和铜水平的可能改变参与了AD的发病机制。
