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

来源：

NEUROBIOLOGY OF DISEASE | 2006年 / 21卷 / 03期

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

页码：618 / 625

页数：8

共 40 条

[1] The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis [J].

Berman, DM ;

Kozasa, T ;

Gilman, AG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (44) :27209-27212

[2] Incipient Alzheimer's disease: Microarray correlation analyses reveal major transcriptional and tumor suppressor responses [J].

Blalock, EM ;

Geddes, JW ;

Chen, KC ;

Porter, NM ;

Markesbery, WR ;

Landfield, PW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (07) :2173-2178

[3] The quantification of gene expression in an animal model of brain ischaemia using TaqMan™ real-time RT-PCR [J].

Bond, BC ;

Virley, DJ ;

Cairns, NJ ;

Hunter, AJ ;

Moore, GBT ;

Moss, SJ ;

Mudge, AW ;

Walsh, FS ;

Jazin, E ;

Preece, P .

MOLECULAR BRAIN RESEARCH, 2002, 106 (1-2) :101-116

[4] High-resolution quantification of specific mRNA levels in human brain autopsies and biopsies [J].

Castensson, A ;

Emilsson, L ;

Preece, P ;

Jazin, E .

GENOME RESEARCH, 2000, 10 (08) :1219-1229

[5] Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis [J].

Castensson, A ;

Emilsson, L ;

Sundberg, R ;

Jazin, E .

BIOLOGICAL PSYCHIATRY, 2003, 54 (11) :1212-1221

[6] Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: Transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling [J].

Colangelo, V ;

Schurr, J ;

Ball, MJ ;

Pelaez, RP ;

Bazan, NG ;

Lukiw, WJ .

JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 70 (03) :462-473

[7] Empirical Bayes analysis of a microarray experiment [J].

Efron, B ;

Tibshirani, R ;

Storey, JD ;

Tusher, V .

JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 2001, 96 (456) :1151-1160

[8] Increased monoamine oxidase messenger RNA expression levels in frontal cortex of Alzheimer's disease patients [J].

Emilsson, L ;

Saetre, P ;

Balciuniene, J ;

Castensson, A ;

Cairns, N ;

Jazin, EE .

NEUROSCIENCE LETTERS, 2002, 326 (01) :56-60

[9] Altered expression of regulators of G-protein signaling (RGS) mRNAs in the striatum of rats undergoing dopamine depletion [J].

Geurts, M ;

Maloteaux, JM ;

Hermans, E .

BIOCHEMICAL PHARMACOLOGY, 2003, 66 (07) :1163-1170

[10]

Ginsberg SD, 2000, ANN NEUROL, V48, P77, DOI 10.1002/1531-8249(200007)48:1<77::AID-ANA12>3.3.CO

← 1 2 3 4 →