Immune-Metabolic Interaction Networks Drive Dementia Risk: Causal Mechanisms and Therapeutic Targets Identified via Mendelian Randomization

This study pioneers a genetic framework connecting immune cells, metabolites, and dementia, positioning metabolites as mediators in the immune-dementia axis. We provide original evidence that immune phenotypes and metabolic pathways exhibit cross-disease synergistic effects, with plasma metabolites acting as an “analytical bridge” translating immune status into dementia risk. These findings offer a genetic foundation for broad-spectrum interventions targeting immune-metabolic hubs. While based on European GWAS data, our results underscore the need for validation in diverse populations.