The potential protective role of peripheral immunophenotypes in Alzheimer’s disease: A Mendelian randomization study

Abstract Background Previous studies have shown that peripheral immune dysregulation plays a paramount role in Alzheimer’s disease (AD), but whether there is a protective causal relationship between peripheral immunophenotypes and AD risk remains ambiguous. Methods Two-sample Mendelian randomization (MR) was performed using large genome-wide association study (GWAS) genetic data to assess causal effects between peripheral immunophenotypes and AD risk. Results This study identified four regulatory T cell (Treg) immunophenotypes—CD25 + + CD45RA- CD4 not regulatory T cell % T cell or CD4 + T cell; Secreting or Activated & secreting CD4 regulatory T cell % CD4 regulatory T cell; monocyte immunophenotype (HLA DR + + monocyte % monocyte); and dendritic cell (DC) subtype (HLA DR on myeloid Dendritic Cell)—that were protective against AD. Discussion These findings enhance the comprehension of the protective role of peripheral immunity in AD and provide further support for Treg and monocyte as potential targets for immunotherapy in AD.