摘要
背景:β-淀粉样蛋白(Aβ)异常累积于阿尔茨海默病(AD)引发者老年斑。作为Aβ降解酶之一,胰岛素降解酶(IDE)在阿尔茨海默氏症大脑的蛋白质水平和活性方面仍存在争议。 方法:对PubMed,EMBASE,Cochrane图书馆,OVID和Sinomed等电子数据库进行系统搜索,直至2017年9月20日。检索已发表的病例对照或队列研究进行Meta分析。 结果:关于IDE蛋白水平(AD病例= 293;对照= 126),3个用于mRNA水平(AD病例= 138;对照= 81)和3个用于酶活性(AD病例= 123;对照= 75)汇集在一起。 AD患者IDE蛋白水平显着低于对照组(SMD = - 0.47,95%CI [-0.69,-0.24],p <0.001),但IDE mRNA和酶活性无显着差异(SMD = 0.02, 95%CI [-0.40,0.43]和SMD = 0.06,95%CI [-0.41,0.53])。亚组分析发现AD病例皮层和海马的IDE蛋白水平均下降(SMD = -0.43,95%CI [-0.71,-0.16],p = 0.002和SMD = -0.53,95%CI [-0.91, -0.15],p = 0.006)。然而,在AD病例皮质中IDE mRNA的表达水平更高(SMD = 0.71,95%CI [0.14,1.29],p = 0.01),而不是在海马(SMD = -0.26,95%CI [-0.58,0.06])。 结论:我们的结果表明AD患者可能具有较低的IDE蛋白酶水平。仍然需要进一步的相关研究来验证IDE是否是影响Aβ异常积聚的因素之一,并为AD的检测或治疗提供新的见解。
关键词: 胰岛素降解酶(IDE),胰岛素,阿尔茨海默病(AD),荟萃分析,痴呆,β-淀粉样蛋白降解酶。
Current Alzheimer Research
Title:Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis
Volume: 15 Issue: 7
关键词: 胰岛素降解酶(IDE),胰岛素,阿尔茨海默病(AD),荟萃分析,痴呆,β-淀粉样蛋白降解酶。
摘要: 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.
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Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis, Current Alzheimer Research 2018; 15 (7) . https://dx.doi.org/10.2174/1567205015666180119105446
DOI https://dx.doi.org/10.2174/1567205015666180119105446 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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