阿尔茨海默病中胰岛素降解酶的特征：一项荟萃分析。

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis.

作者信息

Zhang Huifeng, Liu Dan, Huang Huanhuan, Zhao Yujia, Zhou Hui

机构信息

Department of Occupational and Environmental Health Sciences, Peking University, Beijing, China.

出版信息

Curr Alzheimer Res. 2018;15(7):610-617. doi: 10.2174/1567205015666180119105446.

DOI:10.2174/1567205015666180119105446

PMID:29357797

Abstract

BACKGROUND

β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain.

METHODS

The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis.

RESULTS

Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]).

CONCLUSIONS

Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

摘要

背景

β-淀粉样蛋白（Aβ）异常积聚形成老年斑，老年斑是阿尔茨海默病（AD）的起始因素。作为Aβ降解酶之一，胰岛素降解酶（IDE）在阿尔茨海默病大脑中的蛋白质水平和活性仍存在争议。

方法

系统检索截至2017年9月20日的电子数据库PubMed、EMBASE、Cochrane图书馆、OVID和中国生物医学文献数据库。检索已发表的病例对照研究或队列研究以进行荟萃分析。

结果

汇总了7项关于IDE蛋白水平的研究（AD病例 = 293；对照 = 126）、3项关于mRNA水平的研究（AD病例 = 138；对照 = 81）和3项关于酶活性的研究（AD病例 = 123；对照 = 75）。AD病例中的IDE蛋白水平显著低于对照（标准化均数差[SMD] = -0.47，95%可信区间[-0.69，-0.24]，p < 0.001），但IDE mRNA和酶活性无显著差异（分别为SMD = 0.02，95%可信区间[-0.40，0.43]和SMD = 0.06，95%可信区间[-0.41，0.53]）。亚组分析发现，AD病例的皮质和海马中IDE蛋白水平均降低（分别为SMD = -0.43，95%可信区间[-0.71，-0.16]，p = 0.002和SMD = -0.53，95%可信区间[-0.91，-0.15]，p = 0.006）。然而，AD病例皮质中的IDE mRNA较高（SMD = 0.71，95%可信区间[0.14，1.29]，p = 0.01），海马中则不然（SMD = -0.26，95%可信区间[-0.58，0.06]）。