Causal Associations Between Chronic Inflammatory Skin Diseases and Alzheimer’s Disease: A Bidirectional Two-Sample Mendelian Randomization Study

Background: Inflammatory skin diseases (ISDs) and Alzheimer’s disease (AD) share chronic immune activation, but their causal link remains unclear. Methods: We performed a bidirectional two-sample Mendelian randomization using GWAS summary data from Europeans. Instrumental SNPs were analyzed with inverse-variance weighted (IVW), weighted median, and MR-Egger methods, with sensitivity tests for pleiotropy and heterogeneity. Results: Forward MR revealed significant causal effects of ISDs on AD, including lichen planus (OR 1.318, p=0.005), psoriasis vulgaris (OR 1.126, p=0.004), psoriasis with arthropathy (OR 1.032, p=0.002), psoriatic arthritis (OR 1.053, p=0.016), psoriasis (OR 1.072, p=0.008), papulosquamous conditions (OR 1.046, p=0.007), and follicular cysts (OR 1.066, p=0.047). No heterogeneity or pleiotropy was detected. Reverse analysis showed no causal effect of AD on ISDs. Conclusion: These findings support a potential causal role of chronic skin inflammation in AD risk, though effect sizes were modest and clinical implications remain exploratory. This suggests that neuroimmune mechanisms may represent potential targets for further investigation.