Causal relationship between circulating immune cells and the risk of Alzheimer's disease: A Mendelian randomization study.

BACKGROUND

Increasing evidence has shown a link between immune cells and Alzheimer's disease (AD). Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine the causal association between 731 immune cell signatures and AD in this study.

METHODS

We extracted genetic variants of 731 immune cell traits and AD from the publicly available GWAS dataset. The immune features included median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC) and morphological parameters (MP). The inverse variance weighted (IVW) method was the main MR analysis method, and sensitivity analyses were used to validate the robustness, heterogeneity and horizontal pleiotropy of the results.

RESULTS

After FDR adjustment, seven immune phenotypes were found to be associated significantly with AD risk: HLA DR on CD33HLA DR (OR = 0.938, P = 0.001), Secreting Treg %CD4 (OR = 0.972, P = 0.021), HLA DRT cell AC (OR = 0.928, P = 0.041), Activated & resting Treg % CD4 Treg (OR = 1.031, P = 0.002), CD33 on CD33dim HLA DRCD11b (OR = 1.025, P = 0.025), CD33 on CD14monocyte (OR = 1.026, P = 0.027) and CD33 on CD66bmyeloid cell (OR = 1.027, P = 0.036).

CONCLUSIONS

These findings demonstrated seven immune phenotypes were significantly associated with AD risk. This may provide researchers with a new perspective in exploring the biological mechanisms of AD and may lead to the exploration of earlier treatment.