Peripheral level of CD33 and Alzheimer's disease: a bidirectional two-sample Mendelian randomization study

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Brain CD33 expression is linked to amyloid plaques in Alzheimer's disease (AD).
• The role and peripheral levels of CD33 in AD patients remain unclear.
• Investigating the bidirectional relationship between peripheral CD33 and AD is crucial.

Purpose of the Study:

• To systematically explore the causal relationship between peripheral CD33 and Alzheimer's disease (AD).
• To determine if peripheral CD33 levels influence AD risk.
• To assess if AD influences peripheral CD33 levels.

Main Methods:

• Utilized genome-wide association study (GWAS) datasets for AD and peripheral CD33 (mRNA, protein, immune cell expression).
• Employed Mendelian randomization (MR) analysis, including inverse-variance weighting (IVW) and sensitivity analyses.
• Analyzed data from European populations using R package (V.4.1.2) and TwoSampleMR (v.0.5.5).

Main Results:

• Forward MR analysis showed elevated blood CD33 mRNA and serum protein levels significantly increase AD risk (p < 0.05).
• Increased CD33 expression on immune cell subtypes also correlated with higher AD risk (p < 0.05).
• Reverse MR analysis found no evidence that AD causes elevated peripheral CD33 protein levels (p > 0.05).

Conclusions:

• Elevated peripheral CD33 expression is a causal factor in the development of Alzheimer's disease.
• Peripheral CD33 presents a potential biomarker for AD diagnosis and progression.
• Targeting peripheral CD33 may offer a novel therapeutic strategy for Alzheimer's disease.