LAX1 as a Core Biomarker in Alzheimer's Disease and Periodontitis via the STAT signaling pathway

Abstract

Background: Periodontitis, an inflammatory condition affecting gums and tooth-supporting tissues, is linked to systemic health problems like cardiovascular diseases and Alzheimer's disease, a neurodegenerative disorder causing cognitive decline. The etiology of both conditions remains unclear. Methods: Download Alzheimer's datasets GSE138260 and GSE203206, and periodontitis datasets GSE53849 and GSE173078 from GEO. Utilize Weighted Gene Co-expression Network Analysis to obtain Important modules. Conduct Gene Set Enrichment Analysis to explore biological processes and pathways associated with differentially expressed genes. Apply integrated bioinformatics methods to perform CIBERSORT analysis on merged periodontitis datasets and linear support vector regression for immune cell subtype deconvolution. Validate LAX1's role in periodontitis and Alzheimer's disease through cell experiments using LAX1 overexpression plasmids and silencing siRNA. Assess expression changes in LAX1-related signaling pathways, inflammatory molecules, and apoptosis proteins via western blotting (WB). Results: GSEA results indicate enrichment of differentially expressed genes in apoptosis, neuroregulation, inflammation, neuroactive ligand-receptor interaction, and Jak-STAT signaling pathways. Venn diagram identifies core gene LAX1. Heatmap shows high expression of LAX1 in Alzheimer's and periodontitis samples. WB reveals LAX1 positively correlates with STAT pathway, activating it. Compared to Control group (CON), Glial cells from Alzheimer's disease mice (AD group) and periodontitis groups exhibit elevated IL-1, TNF-α, and IL-6, exacerbating inflammation with increased LAX1 expression. Conversely, inflammation decreases. This suggests LAX1 promotes inflammation. Compared to CON, AD and groups show downregulation of P53, Caspase-3, and FAS. Upregulation of LAX1 leads to increased expression of P53, Caspase-3, and FAS, promoting apoptosis. Conversely, apoptosis slows down. These results indicate LAX1 promotes apoptosis. Conclusion: LAX1 may serve as a core biomarker in Alzheimer's disease and periodontitis. LAX1 activates the STAT signaling pathway, promoting inflammatory responses and apoptosis.