Causal relationships between plasma proteins and Alzheimer's disease using bidirectional Mendelian randomization

Area of Science:

• Neuroscience
• Genetics
• Biochemistry

Background:

• Alzheimer's disease (AD) pathogenesis involves complex genetic, immune, and metabolic interactions.
• Identifying causal plasma proteins can elucidate AD pathways and reveal therapeutic targets.

Purpose of the Study:

• To investigate causal relationships between Alzheimer's disease (AD) and plasma protein levels.
• To explore both forward (protein to AD) and reverse (AD to protein) causal effects.

Main Methods:

• A two-stage, two-sample Mendelian randomization (MR) analysis was performed.
• Genome-wide association study datasets for plasma proteins and AD were utilized.
• Non-overlapping datasets ensured robust and independent analyses.

Main Results:

• Twenty-five plasma proteins demonstrated causal associations with Alzheimer's disease (AD).
• Many identified proteins are involved in immune and lipid metabolic pathways.
• Findings support the role of inflammation and lipid metabolism in AD.

Conclusions:

• This research strengthens the link between immune and lipid dysregulation in AD.
• Identified proteins may serve as novel biomarkers or therapeutic targets for AD.
• Advances understanding of molecular mechanisms in AD progression.