Causal Association between Circulating Metabolites and Dementia: A Mendelian Randomization Study
Hong-Min Li1, Cheng-Shen Qiu1, Li-Ying Du1
1Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Nutrients
|September 14, 2024
Summary
Circulating metabolites, particularly lipids and HDL particle traits, show causal links to dementia risk. These findings identify potential biomarkers and therapeutic targets for preventing dementia.
Area of Science:
- Genetics and Epidemiology
- Metabolomics
- Neurodegenerative Diseases
Background:
- The relationship between circulating metabolites and dementia risk is not fully understood.
- Identifying causal factors is crucial for developing effective dementia prevention and treatment strategies.
Purpose of the Study:
- To investigate the causal associations between circulating metabolites and the risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD).
- To identify specific metabolites and metabolic pathways implicated in dementia pathogenesis.
- To explore potential predictive biomarkers and therapeutic targets for dementia.
Main Methods:
- Utilized Mendelian randomization (MR) analysis with a large dataset of 486 metabolites.
- Performed univariable MR for dementia, AD, and VaD risk, with secondary validation using 123 metabolites.
- Employed Bayesian model averaging MR (MR-BMA) and pathway analysis for metabolite prioritization and pathway identification.
Main Results:
- Identified 118 metabolites associated with dementia risk, with 59 being lipids, highlighting their role in pathogenesis.
- Discovered nine HDL particle traits as potential causal mediators of dementia.
- Found protective effects of epiandrosterone sulfate on AD and glycoproteins on VaD. MR-BMA identified HDL particle size and concentration as key protective factors.
Conclusions:
- Circulating metabolites, especially lipids and HDL particle characteristics, are causally associated with dementia risk.
- Specific metabolites and metabolic pathways offer promising avenues for dementia biomarker discovery and therapeutic intervention.
- Findings support the role of lipid metabolism and HDL function in dementia prevention.
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