Showing NAFLD, as a key connector disease between Alzheimer’s disease and diabetes, via systems biology analysis

This study was designed to perform network analysis of Alzheimers҆ disease and diabetes and to find their correlation with each other and other diseases/pathways.

Alzheimer’s disease (AD) as a neurodegenerative disease and diabetes as a metabolic disease are two major health problems in the recent years. The recent studies have reported their correlation and same spreading pathways of these two diseases together, but details of this relation are not well known yet at molecular level..

In thermal proteome profiling (TPP) technique, after treatment of the extracted proteins by heat and drug concentration, the resulting proteins were analyzed by mass spectrometry. Enrichment analysis of these proteins led to development of AD and diabetes. First, corresponding genes for each disease were extracted from DisGeNET database and then, protein-protein interaction network was constructed for each of them using the search tool for retrieval of interacting genes and proteins (STRING). After analyzing these networks, hub-bottleneck nodes of networks were evaluated. Also, common nodes between two networks were extracted and used for further analysis.

High correlation was found between AD and diabetes based on the existence of 40 common genes. Results of analyses revealed 14 genes in AD and 12 genes in diabetes as hub-bottleneck 7 of which were common including caspase 3 (CASP3), insulinlike growth factor 1 (IGF1), catalase (CAT), tumor necrosis factor (TNF), leptin (LEP), vascular endothelial growth factor A (VEGFA), and interleukin 6 ( IL-6).

Our results revealed a direct correlation between AD and diabetes and also a correlation between these two diseases and non-alcoholic fatty liver disease (NAFLD), suggesting that a small change in each of these three diseases can lead to development of any other diseases in the patients. Also, the enrichments exhibited the existence of common pathways between AD, diabetes, NAFLD, and male infertility.