Up-regulation of calcineurin Abeta mRNA in the Alzheimer's disease brain: assessment by cDNA microarray.
Recent advances in cDNA microarray technology have made it possible to analyze expression of more than 8000 genes. Using this technology, gene expression in the hippocampus containing neurofibrillary tangle-associated lesions from an Alzheimer's disease (AD) patient was compared with expression in the parietal cortex from the same patient that lacked these lesions. We also compared gene expression using a control brain. The top 20 named genes significantly up-regulated or down-regulated only in the AD brain were determined. The most up-regulated gene proved to be calcineurin Abeta mRNA (CAbeta). In situ hybridization histochemistry revealed that CAbeta was significantly up-regulated in pyramidal neurons of the hippocampus in the AD brain. RT-PCR analysis revealed that CAbeta was up-regulated in the hippocampus from two out of three AD brains while there were no changes in three control brains. Our study suggests that CAbeta may play a crucial role in the pathophysiological mechanisms in AD.
Hata
R
R
BF Research Institute, c/o National Cardiovascular Center, 5-7-1, Fujishiro-dai, Suita, Osaka, 565-0873, Japan. hata@m.ehime-u.ac.jp
Masumura
M
M
Akatsu
H
H
Li
F
F
Fujita
H
H
Nagai
Y
Y
Yamamoto
T
T
Okada
H
H
Kosaka
K
K
Sakanaka
M
M
Sawada
T
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D007527:Isoenzymes; D012333:RNA, Messenger; D019703:Calcineurin