Tao Yunlong, Wang Yu, Rogers Jack T, Wang Fudi
Laboratory of Nutrition and Metabolism, Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J Alzheimers Dis. 2014;42(2):679-90. doi: 10.3233/JAD-140396.
The homeostasis and physiological role of iron in Alzheimer's disease (AD) has been debated for decades. Overall, it has been difficult to reach a consensus to prove marked disease-associated changes in the iron content of the AD brain, blood, or cerebrospinal fluid (CSF).
We sought to contribute to resolve this issue by quantifying the iron content in serum, CSF, and sub-regions of the AD brain.
We conducted a comprehensive systematic meta-analysis and review of multiple observational studies till October 2013 that investigated the iron content in AD serum, CSF, or brain tissue.
2,556 publications were screened. Forty-three eligible studies with 1,813 AD patients and 2,401 healthy controls were identified. Twenty-one studies investigated the serum iron in AD while seven and nineteen studies investigated the CSF iron and various brain regions iron respectively. Our meta-analysis showed that serum iron was significant lower in AD than healthy controls. CSF iron appeared not to be affected by AD although more studies are required due to the relative small number of CSF studies reported to date. We critically analyzed iron content in twelve selective brain regions by separated meta-analyses using cross-referenced statistical methods. We found that eight specific brain regions had higher iron concentrations that correlated with the clinical diagnosis of AD in a statistically validated manner.
These data provided rigorous statistical support for the model that iron homeostasis was changed in AD patients, including the finding of lower iron in their serum and evidence for iron overload in several specific brain regions.
铁在阿尔茨海默病（AD）中的稳态及生理作用已争论了数十年。总体而言，很难就AD患者大脑、血液或脑脊液（CSF）中铁含量存在与疾病显著相关的变化达成共识。
我们试图通过量化血清、脑脊液及AD大脑亚区域的铁含量来推动解决这一问题。
我们对截至2013年10月的多项观察性研究进行了全面系统的荟萃分析及综述，这些研究调查了AD血清、脑脊液或脑组织中的铁含量。
共筛选了2556篇出版物。确定了43项符合条件的研究，涉及1813例AD患者和2401例健康对照。21项研究调查了AD患者的血清铁，7项和19项研究分别调查了脑脊液铁和不同脑区的铁。我们的荟萃分析表明，AD患者的血清铁显著低于健康对照。脑脊液铁似乎不受AD影响，不过由于迄今报道的脑脊液研究数量相对较少，仍需要更多研究。我们使用交叉参考统计方法，通过单独的荟萃分析对12个选择性脑区的铁含量进行了批判性分析。我们发现，8个特定脑区的铁浓度较高，且与AD的临床诊断存在经统计学验证的相关性。
这些数据为AD患者铁稳态发生变化的模型提供了严格的统计学支持，包括血清铁降低的发现以及几个特定脑区铁过载的证据。
