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阿尔茨海默病患者大脑中胰岛素受体底物(INSR)、衔接蛋白β2(APBA2)和胰岛素降解酶(IDE)基因表达的变化

Change in INSR, APBA2 and IDE Gene Expressions in Brains of Alzheimer's Disease Patients.

作者信息

da Costa Isabela Bazzo, de Labio Roger Willian, Rasmussen Lucas Trevizani, Viani Gustavo Arruda, Chen Elizabeth, Villares Joao, Turecki Gustavo, Smith Marilia de Arruda Cardoso, Payao Spencer L M

机构信息

Marília School of Medicine (Faculdade de Medicina de Marília), Marília Sao Paulo. Brazil.

Universidade do Sagrado Coracao, Bauru, Sao Paulo. Brazil.

出版信息

Curr Alzheimer Res. 2017;14(7):760-765. doi: 10.2174/1567205014666170203100734.

DOI:10.2174/1567205014666170203100734
PMID:28164769
Abstract

BACKGROUND

Alzheimer's disease (AD) is defined as a progressive and irreversible neurodegenerative disorder, the onset of which is mainly characterized by decreased cognition, memory loss, and mental confusion.

OBJECTIVE

This study sought to quantify mRNA expression of the APBA2, INSR and IDE genes in brain samples from patients with AD and controls.

METHODS

We investigated the mRNA expression of the APBA2, INSR and IDE genes in 150 RNA samples from entorhinal cortex, auditory cortex, and the hippocampus of individuals with AD and elderly controls using real time PCR. APOE genotypes were determined by PCR-RFLP.

RESULTS

When the total brain samples were analyzed collectively, a decrease in IDE gene expression was found in AD patients relative to healthy elderly controls. However, when the samples were analyzed separately according to the region of the brain, there was a significant upregulation of INSR expression in the hippocampus and the entorhinal cortex in the AD patient group. We did not observe any statistical differences when gene expression was compared in the different regions of the brain of AD patients. When the E4 allele of apolipoprotein-E was considered in AD patients, the presence of this allele was found to be associated with decreased APBA2 gene expression. The same analysis using the INSR and IDE genes showed no significant statistical differences.

CONCLUSION

These results support the hypothesis that APBA2, IDE, and particularly INSR gene expression in different areas of Alzheimer's patient's brains could represent new markers for use in clinical diagnoses in the near future.

摘要

背景

阿尔茨海默病(AD)被定义为一种进行性且不可逆的神经退行性疾病,其发病主要特征为认知能力下降、记忆力丧失和精神错乱。

目的

本研究旨在量化AD患者和对照者脑样本中APBA2、INSR和IDE基因的mRNA表达。

方法

我们使用实时PCR研究了150份来自AD患者和老年对照者的内嗅皮质、听觉皮质和海马体的RNA样本中APBA2、INSR和IDE基因的mRNA表达。通过PCR-RFLP确定APOE基因型。

结果

对全脑样本进行综合分析时,发现AD患者的IDE基因表达相对于健康老年对照者有所下降。然而,当根据脑区分别分析样本时,AD患者组的海马体和内嗅皮质中INSR表达显著上调。在比较AD患者不同脑区的基因表达时,我们未观察到任何统计学差异。在AD患者中考虑载脂蛋白E的E4等位基因时,发现该等位基因的存在与APBA2基因表达降低有关。对INSR和IDE基因进行同样的分析未显示出显著的统计学差异。

结论

这些结果支持以下假设,即阿尔茨海默病患者大脑不同区域的APBA2、IDE,尤其是INSR基因表达可能在不久的将来成为临床诊断的新标志物。

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