Potential association between allergic disease and risk of Alzheimer's disease: insight from genetic analysis

Numerous evidence from observational studies indicated an association between allergic diseases and Alzheimer's Disease (AD). However, the causal association of this relationship remains unclear. To address this, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the potential causal impact of allergic diseases on AD.

We used summary statistics for allergic diseases (allergic rhinitis, asthma, and atopic dermatitis) and AD from comprehensive genome-wide association studies (GWASs). Our primary analytical approach was inverse variance weighted (IVW) method, complemented by MR-Egger method and weighted median (WM) method.

In the forward MR analysis, our results indicate that age of onset of asthma is a protective factor against AD (OR = 0.824, 95% CI: 0.736-0.922, P < 0.001). However, we found no causal link between the age of onset of childhood onset asthma (OR = 1.023, 95% CI: 0.955-1.095, P = 0.510), allergic rhinitis (OR = 0.609, 95% CI: 0.188-1.973, P = 0.408) or atopic dermatitis (OR = 1.000, 95% CI: 0.995-1.005, P = 0.902) and AD risk. The sensitivity analysis confirms the robustness of our findings. In the reverse MR analysis, our results suggest that asthma has a bidirectional association with AD (OR = 0.994, 95% CI: 0.990-0.997, P < 0.001).

Our study suggests that age of onset of asthma may reduce genetic susceptibility to AD. In addition, AD appear more likely to develop asthma risk. However, no significant genetic correlations were observed between allergic rhinitis or atopic dermatitis with AD risk.