Identification of the common pathogenesis of Alzheimer’s and nonalcoholic fatty liver disease and exploration of their relationship with immune cells

Abstract

Alzheimer’s disease (AD) and nonalcoholic fatty liver disease (NAFLD) are both prominent public health concerns owing to their increasing prevalence and burden on healthcare systems. The interconnected genetic and immunological mechanisms that may cause both of these diseases are poorly understood. This study used broad gene expression datasets to identify similar molecular markers and immunological profiles in AD and NAFLD and evaluate their potential. Using the Gene Expression Omnibus (GEO) database, mRNA expression profiles from patients with AD and NAFLD were analyzed alongside control samples to identify differentially expressed genes (DEGs). Systems biology approaches, including LASSO regression and multivariate logistic regression models, were used to further refine the significance of DEGs. The diagnostic potential of the key genes was evaluated using receiver operating characteristic (ROC) curves, and the immune cell environment was quantified using the Immune Cell Abundance Identifier (ImmuCellAI). We identified 11,278 DEGs, with 3551 upregulated and 7857 downregulated genes. S100A8, CXCL9, and ST8SIA3 have emerged as significant biomarkers of both AD and NAFLD. ROC analysis substantiated the diagnostic value of these markers. Additionally, distinct patterns of immune cell populations have been observed in AD and NAFLD, highlighting potential targets for immunomodulatory therapy. This study elucidates shared molecular and immune mechanisms in AD and NAFLD, offering insights into the pathophysiological underpinnings that could inform the development of novel diagnostic and therapeutic strategies. S100A8, CXCL9, and ST8SIA3 are potential candidates for future clinical application. Further investigation into these genetic discoveries and their immune system effects may lead to a unified strategy for treating these complicated disorders.