Alzheimer's disease: mRNA expression profiles of multiple patients show alterations of genes involved with calcium signaling
Alzheimer's disease: mRNA expression profiles of multiple patients show alterations of genes involved with calcium signaling
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DOI：
10.1016/j.nbd.2005.09.004
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发表时间：
2006-03-01
影响因子：
6.1
通讯作者：
Jazin, E
中科院分区：
文献类型：
--
作者：
Emilsson, L;Saetre, P;Jazin, E
我们结合了全球和高分辨率的策略，在有史以来研究的最大的阿尔茨海默病患者和对照组脑尸检中发现了mRNA表达水平改变的基因。我们的全球分析涉及从114个个体获得的大样本池的微阵列杂交，使用两组独立的微阵列。从微阵列实验中选择的10个基因分别使用实时RT-PCR对每个个体进行定量。这种高分辨率分析解释了年龄、死后间隔、大脑pH值和参考基因表达的系统差异，并估计了疾病对mRNA水平的影响，以及所有其他变量的影响。10个基因中有8个基因的差异表达得到证实。其中，B型1，4，5-三磷酸肌醇3-激酶（ITPK B）和G蛋白信号转导调节因子4（RGS 4）在患者中的表达水平高度改变（P值< 0.0001）。我们的研究结果指向增加肌醇三磷酸（IP 3）介导的钙信号在阿尔茨海默病。(C)2005年爱思唯尔公司All rights reserved.
We combined global and high-resolution strategies to find genes with altered mRNA expression levels in one of the largest collection of brain autopsies from Alzheimer's patients and controls ever studied. Our global analysis involved microarray hybridizations of large pools of samples obtained from 114 individuals, using two independent sets of microarrays. Ten genes selected from the microarray experiments were quantified on each individual separately using real-time RT-PCR. This high-resolution analysis accounted for systematic differences in age, postmortem interval, brain pH, and reference gene expression, and it estimated the effect of disease on mRNA levels, on top of the effect of all other variables. Differential expression was confirmed for eight out of ten genes. Among them, Type B inositol 1,4,5-trisphosphate 3-kinase (ITPKB), and regulator of G protein signaling 4 (RGS4) showed highly altered expression levels in patients (P values < 0.0001). Our results point towards increased inositol triphospate (IP3)-mediated calcium signaling in Alzheimer's disease. (C) 2005 Elsevier Inc. All rights reserved.