Investigation of the potential connections between NAFLD-associated Alzheimer's disease: bioinformatics analysis of shared genes

Abstract

NAFLD has some potential risk factors for developing Alzheimer's disease. This study attempted to establish the potential connections between NAFLD-associated Alzheimer's disease (AD) by analyzing shared genes and pathways using bioinformatics tools. Initially, prepared gene lists related to AD and NAFLD were collected from the GeneCard database, and genes with GeneCard relevance score ≥ 20 were extracted to make a new gene list. The Venn diagram identified common genes (417) between the two diseases from the new gene list. The common genes were used for further analysis of the PPI network, which was constructed using the STRING database with a minimum required interaction score ≥ 0.9 to obtain network relationships. The networks had shown 397 nodes, 1210 edges, an average node degree of 54.7, and an expected number of edges at 397. The top 25 hub genes were calculated by Cytoscape (vs3.10.2) using the bottleneck, degree, and closeness method using CytoHubba. The merged network of the top 25 hub genes from the previously mentioned three methods was contracted to identify the connection between NAFLD and AD. Our study revealed that important pathways were PI3K-Akt and AGE-RAGE in diabetic complications, NAFLD-related systemic inflammation to neuroinflammation, and LRP-1-induced amyloid and tau hyperphosphorylation. This suggests an interrelation between the two major diseases, ushering in the need for new possibilities utilizing this crosstalk.