Causal relationships between peripheral immune cells and Alzheimer's disease: a two-sample Mendelian randomization...

Area of Science:

• Immunology
• Neuroscience
• Genetics

Background:

• Peripheral immune cells are increasingly implicated in neurodegenerative diseases.
• The specific contribution of peripheral immune cell composition to Alzheimer's disease (AD) pathogenesis remains unclear.

Purpose of the Study:

• To investigate the causal relationship between peripheral immune cell composition and the risk of developing AD.
• To identify specific immune cell types associated with increased or decreased AD susceptibility.

Main Methods:

• A two-sample Mendelian randomization (MR) approach was employed to assess the association between peripheral immune cells and AD.
• Primary analysis utilized the inverse variance weighted (IVW) method, with supporting analyses from MR-Egger, weighted median, and mode-based methods.
• Heterogeneity and horizontal pleiotropy were assessed using Cochran's Q statistics and the MR-Egger intercept.

Main Results:

• Increased IgD+CD24- AC cells, CD4+ %leukocyte, and CD4+CD8dim AC cells were significantly associated with higher AD susceptibility (ORs ranging from 1.03 to 1.08).
• Conversely, increased EM DN (CD4-CD8-) %T cells and DN (CD4-CD8-) AC cells showed a protective effect against AD (ORs of 0.95 and 0.93, respectively).

Conclusions:

• This study provides the first evidence of a causal link between peripheral immune cell composition and AD using MR.
• Findings highlight specific immune cell populations as potential biomarkers for AD risk and therapeutic targets.