IL7R ⁺ T Cell‐Macrophage Crosstalk Links Asthma to Alzheimer's Pathogenesis: Integrating Mendelian Randomization and CellChat Analysis

The impact of moderate to severe asthma on AD risk persisted (OR_IVW= 1.01, 95% CI = 1.00-1.02, p = 3.85 × 10^-3) after controlling for confounder risk factors in multivariable MR analyses. Additionally, the study showed that 1.8% of the total effect (moderate to severe asthma) was mediated by eosinophils. SMR analysis and the gene-wide MR analysis revealed numerous gene targets linked to the susceptibility of AD and moderate to severe asthma. Among these targets, FPR1 (Formyl Peptide Receptor 1), IL1RAP (Interleukin 1 Receptor Accessory Protein), IL7R (Interleukin 7 Receptor), and IL18RAP (Interleukin 18 Receptor Accessory Protein) warrant additional exploration as potential therapeutic targets for AD and moderate to severe asthma. LDSC analysis revealed no significant overlap between asthma and AD (rg = 0.0436, SE = 0.0813, p = 0.592), suggesting distinct genetic architectures. Integrated single-cell RNA sequencing analysis of asthma PBMCs and AD CSF revealed IL7R may utilize the MIF-CD74-CXCR4 pathway to complete crosstalk between CD4 T cells and macrophages and contribute to AD disease development.