Perturbed iron distribution in Alzheimer's disease serum, cerebrospinal fluid, and selected brain regions: a systematic review and meta-analysis.
Perturbed iron distribution in Alzheimer's disease serum, cerebrospinal fluid, and selected brain regions: a systematic review and meta-analysis.
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DOI：
10.3233/jad-140396
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发表时间：
2014
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影响因子：
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通讯作者：
Yunlong Tao;Yu Wang;J. Rogers;Fudi Wang
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文献类型：
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作者：
Yunlong Tao;Yu Wang;J. Rogers;Fudi Wang
背景铁在阿尔茨海默病（AD）中的稳态和生理作用已经争论了几十年。总体而言，很难达成共识来证明AD大脑、血液或脑脊液（CSF）中的铁含量存在明显的疾病相关变化。我们试图通过定量血清、CSF和AD脑亚区域中的铁含量来解决这个问题。方法我们对截至2013年10月的多项观察性研究进行了全面系统的荟萃分析和审查，这些研究调查了AD血清，CSF或脑组织中的铁含量。结果筛选了2,556篇出版物。确定了43项符合条件的研究，其中包括1，813名AD患者和2，401名健康对照。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CSF铁和不同脑区铁。我们的荟萃分析表明，血清铁显着低于AD比健康对照组。CSF铁似乎不受AD的影响，但由于迄今为止报告的CSF研究数量相对较少，因此需要进行更多的研究。我们批判性地分析了铁含量在12个选择性的大脑区域的独立的荟萃分析，使用交叉引用的统计方法。我们发现，八个特定的大脑区域具有较高的铁浓度，这与AD的临床诊断相关。结论：这些数据为AD患者铁稳态改变的模型提供了严格的统计学支持，包括发现血清中的低铁和几个特定脑区铁过载的证据。
BACKGROUND 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). OBJECTIVES We sought to contribute to resolve this issue by quantifying the iron content in serum, CSF, and sub-regions of the AD brain. METHODS 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. RESULTS 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. CONCLUSIONS 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.