medRxiv : the preprint server for health sciences · 2026
Exposome contribution to the brain metabolome: importance of body brain connection.
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Karu Naama, Zhao Haoqi Nina, Batra Richa, Arnold Matthias, Krumsiek Jan, David Lurian Caetano, Barupal Dinesh, Schimmel Leyla, Kueider-Paisley Alexandra, Blach Colette, Borkowski Kamil, Dorrestein Pieter, Bennett David A, Kaddurah-Daouk Rima, Alzheimer’s Disease Metabolomics Consortium
Аннотация
INTRODUCTION: Mounting evidence support exposome influences on brain function and health, complementing genome influences. Understanding the molecular imprint of exposome on brain metabolism and the biochemical communication between the body and brain can impact our fundamental understanding and treatment of neuropsychiatric diseases.
METHODS: Leveraging two complementary metabolomics platforms, we classified 1400 features in 514 brains from the ROSMAP collection. We evaluated the origin of these compounds using literature and databases. We correlated those metabolites with cognitive function using linear models.
RESULTS: We identified over 230 non-endogenous compounds in the brain, including 103 drugs and metabolites, 120 dietary and microbial products and possibly 15 compounds from environmental exposures. Over 20 dietary and gut microbial compounds showed associations with cognition.
DISCUSSION: Comprehensive profiling of chemicals in the brain and the link to cognitive function provides foundational work to connect body and brain in the study of AD and related dementias.
METHODS: Leveraging two complementary metabolomics platforms, we classified 1400 features in 514 brains from the ROSMAP collection. We evaluated the origin of these compounds using literature and databases. We correlated those metabolites with cognitive function using linear models.
RESULTS: We identified over 230 non-endogenous compounds in the brain, including 103 drugs and metabolites, 120 dietary and microbial products and possibly 15 compounds from environmental exposures. Over 20 dietary and gut microbial compounds showed associations with cognition.
DISCUSSION: Comprehensive profiling of chemicals in the brain and the link to cognitive function provides foundational work to connect body and brain in the study of AD and related dementias.