Genes related to microglia polarization and immune infiltration in Alzheimer’s Disease

Alzheimer’s Disease (AD) remains a significant challenge due to its complex etiology and socio-economic burden. In this study, we investigated the roles of macrophage polarization-related hub genes in AD pathology, focusing on their impact on immune infiltration and gene regulation in distinct brain regions. Using Gene Expression Omnibus (GEO) datasets GSE110226 (choroid plexus) and GSE1297 (hippocampal CA1), we identified key genes—EDN1, HHLA2, KL, TREM2, and WWTR1—associated with AD mechanisms and immune responses. Based on these findings, we developed a diagnostic model demonstrating favorable calibration and clinical applicability. Furthermore, we explored molecular interactions within mRNA-transcription factor and mRNA-miRNA regulatory networks, providing deeper insights into AD progression and identifying potential therapeutic targets. The novel identification of WWTR1 and HHLA2 as biomarkers expands the diagnostic toolkit for AD, offering new perspectives on the disease’s underlying immune dynamics. However, external dataset validation and further in vitro and in vivo studies are required to confirm these results and their clinical relevance.