Alzheimer's disease and antibody-mediated immune responses to infectious diseases agents: A mendelian randomization study

Background Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, with antibody-mediated immune responses to infectious diseases agents potentially playing a decisive role in its pathophysiological process. However, the causal relationship between antibodies and AD remains unclear. Methods A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal link between antibody-mediated immune responses to infectious diseases agents and the risk of AD. Genetic variations associated with these antibodies and data on AD were both obtained from the UK Biobank, utilizing its extensive repository of genome-wide association studies (GWAS) for a comprehensive analysis. The MR analysis employed the inverse variance-weighted, MR-Egger, and weighted median methods. Sensitivity analysis was also performed using MR-Egger regression, MR-pleiotropy residual sum, and outlier tests. Results Seven causal associations were identified between antibody-mediated immune responses to infectious diseases agents and AD. Anti-polyomavirus 2 IgG, Polyomavirus 2 JC VP1 antibody, anti-Merkel cell polyomavirus IgG, and anti-varicella zoster virus IgG and varicella zoster virus glycoproteins E and I antibody suggest a protective association with AD. Conversely, higher levels of Toxoplasma gondii p22 and Epstein-Barr virus EBNA-1 antibody appear to be associated with an increased risk of AD. Conclusion Our MR analysis has revealed a causal relationship between antibody-mediated immune responses to specific infectious disease agents and AD. These findings provide valuable insights into the pathophysiological mechanisms underlying AD.