Alzheimer's disease: mRNA expression profiles of multiple patients show alterations of genes involved with calcium signaling

被引:93
作者
Emilsson, L [1 ]
Saetre, P [1 ]
Jazin, E [1 ]
机构
[1] Uppsala Univ, Dept Evolut Genom & Systemat, S-75236 Uppsala, Sweden
关键词
D O I
10.1016/j.nbd.2005.09.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:618 / 625
页数:8
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