COMMON PATHWAYS BETWEEN AGING AND ALZHEIMER’S DISEASE REVEALED BY SYSTEMS-BIOLOGICAL APPROACH

Abstract

Alzheimer's disease (AD) is one of the neurodegenerative diseases occurring over 65 years old. Aging is a risk factor of AD. Systems-biological analysis is potential tool for integration of biological information, for example on the pathogenesis of diseases. In particular, gene expression and protein-protein interaction (PPI) analysis have been very powerful in finding target molecules for the treatment of diseases. To identify therapeutic target molecules and biological pathways of AD and brain aging process, we have done PPI network analysis of proteins using microarray big data. Bioinformatics approaches including microarray analysis, transcription factor binding site prediction, and protein–protein interaction (PPI) network analysis were used in this study. We identified about 300 genes that were significantly differently expressed in the brain tissues of patients with AD and normal aging process. To identify hub molecules, we tried PPI analysis. The PPI network was found to include 27 molecules, which were found to be related to ‘hematopoietic cell lineage’, ‘cytokine-cytokine receptor interaction’, and ‘Jak-STAT signaling pathway’. These pathways might be important in the progression of AD and brain aging. In particular, the Jak-STAT signaling pathway, which is known to play a critical role in AD development, was up-regulated in both AD and aging. SOCS3, IL4R, and CSF3R were up-regulated, which was found to be involved in the Jak-STAT signaling pathway. Furthermore, the current study on RNA-Seq analysis of aged hippocampus revealed that pro-inflammatory genes were upregulated in brain aging process. Cytokine-cytokine interaction and Jak-STAT signaling pathway play an important role in the common mechanisms underlying both AD and brain aging. These systems-biological approach is powerful tool for discovery of new key molecules involved in AD.