BackgroundAlzheimer's disease (AD) is a debilitating neurodegenerative disorder. Although peripheral immune cells have been implicated in the pathology of AD, the causal relationship between peripheral blood immune cells and AD remains to be fully elucidated.ObjectiveTo examine the association between peripheral blood immune cell phenotypes and AD, mediated by peripheral blood metabolite, a two-step Mendelian randomization (MR) analysis was performed.MethodsSummary statistics were obtained from the two largest independent cohorts. We explored bidirectional univariable MR analysis to explore causal associations and assessed the mediated proportion of peripheral blood metabolite phenotypes.ResultsThe proportion of IgD + CD38- B cells (Bm1) were found to increase the risk of AD in both the FinnGen database (