Application of Mendelian Randomization Analysis on the Exploration of the Association Between Immune Cell Phenotypes and Alzheimer's disease

This study explores the correlation between immune inflammation and Alzheimer's disease (AD), focusing on immune-brain interactions impacting neurodevelopment and function. Public genetic data were used to analyze 731 immune cell signals, employing two-sample Mendelian randomization, with multiple testing corrected by the Bonferroni-adjusted false discovery rate (FDR). Six immune phenotypes were identified as significantly increasing AD risk (effect sizes ranging from OR=1.038 to 1.123), including HLA DR on CD33+ HLA DR+ CD14-, HLA DR on CD14+ monocyte, CD4+ CD8dim T cells (% lymphocytes), CD33 on HLA DR on CD14+ CD16- monocyte, CD33 on CD33+ HLA-DR+ CD14dim cells and CD11c on CD62L+ myeloid dendritic cell. This study confirms the genetic association between specific immune cells and AD, highlighting potential immune-related biomarkers for AD risk.