Alzheimer’s disease: mRNA expression profiles of multiple patients show alterations of genes involved with calcium signalling
2006 (English)In: Neurobiology of Disease, ISSN 0969-9961, E-ISSN 1095-953X, Vol. 21, no 3, 618-625 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2006. Vol. 21, no 3, 618-625 p.
Aged, Aged; 80 and over, Alzheimer Disease/*genetics, Calcium Signaling/*genetics, Female, Gene Expression, Gene Expression Profiling, Humans, In Situ Hybridization, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, RNA; Messenger/analysis, Reverse Transcriptase Polymerase Chain Reaction
IdentifiersURN: urn:nbn:se:uu:diva-93407DOI: 10.1016/j.nbd.2005.09.004PubMedID: 16257224OAI: oai:DiVA.org:uu-93407DiVA: diva2:166871