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 A beta mRNA (CA beta). In situ hybridization histochemistry revealed that CA beta was significantly up-regulated in pyramidal neurons of the hippocampus in the AD brain. RT-PCR analysis revealed that CA beta 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 CA beta may play a crucial role in the pathophysiological mechanisms in AD.