Multi-Scale Integrative Transcriptomic Analysis of Alzheimer's Disease and Atopic Dermatitis Reveals Shared Immune and Cellular Networks.

Abstract

BackgroundAlzheimer's disease and atopic dermatitis may converge on shared immunoinflammatory pathways, but their molecular relationship remains poorly defined.MethodsWe integrated differential expression, enrichment analysis, network prioritization, machine learning, external dataset assessment, and Mendelian randomization to identify shared molecular signatures and assess their causal relevance. Single-cell transcriptomics, cell-cell communication analysis, virtual knockout, and molecular simulation were further applied to define cell-type-specific signaling networks and evaluate drug-target interactions.ResultsIntegrative transcriptomic analyses identified MYD88 and FGR as hub genes linking immune activation with structural regulation. Convergent evidence highlighted the IgSF CAM signaling pathway, suggesting that impaired cell adhesion and intercellular communication represent a common pathological feature of both diseases. Single-cell analyses revealed distinct microenvironmental signaling landscapes, characterized by NRG-ERBB4 activity in Alzheimer's disease and MIF-centered immune networks in atopic dermatitis.ConclusionsThese findings suggest potential shared immune-structural regulatory features between Alzheimer's disease and atopic dermatitis.