Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology.

ABSTRACT: The gut microbiome modulates metabolic, immune, and neurological functions and has been implicated in Alzheimer's disease (AD), though the specific mechanisms remain poorly defined. The bacterial metabolite imidazole propionate (ImP) has been previously associated with several AD comorbidities, such as type 2 diabetes and cardiovascular disease. Here, we show that elevated plasma ImP levels are associated with lower cognitive scores and AD biomarkers in a cohort of >1,100 cognitively unimpaired individuals. Metagenomic profiling identified gut bacteria encoding putative orthologs of the ImP-synthesizing enzyme, urocanate reductase (UrdA), whose abundance correlated with both cognitive measures and multiple AD biomarkers. Chronic ImP administration to mice activated neurodegenerative pathwa

SUBMITTER: Vemuganti V 

PROVIDER: S-EPMC12157550 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature