A Multi-Organ Murine Metabolomics Atlas Reveals Molecular Dysregulations in Alzheimer's Disease DOI Creative Commons
Simone Zuffa, Celeste Allaband, Vincent Charron‐Lamoureux

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

SUMMARY The etiology of Alzheimer’s Disease (AD) remains largely unclear but is likely driven by gene-environment interactions. Here, we present a multi-organ untargeted metabolomics dataset (2,271 samples) generated from five tissue types in two genetic AD mouse models under colonized or germ-free conditions, complemented shotgun metagenomics sequencing data (666 samples). Systems-level analyses 3xTg and 5xFAD mice reveal clusters dysregulated molecular classes across tissues including carnitines, bile acids, B vitamins, neurotransmitters. This signature, coupled with microbiome profiles, suggests increased oxidative stress via mitochondrial dysfunction. Molecular feature tracking tissueMASST, mass spectrometry search tool developed to bridge animal model findings human data, identifies microbially-modulated phenylacetyl-carnitine as positively associated aging cognitive impairment studies. With hundreds yet-to-be-characterized metabolites, this public resource its tools will aid future research the pathophysiology AD.

Language: Английский

A Multi-Organ Murine Metabolomics Atlas Reveals Molecular Dysregulations in Alzheimer's Disease DOI Creative Commons
Simone Zuffa, Celeste Allaband, Vincent Charron‐Lamoureux

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

SUMMARY The etiology of Alzheimer’s Disease (AD) remains largely unclear but is likely driven by gene-environment interactions. Here, we present a multi-organ untargeted metabolomics dataset (2,271 samples) generated from five tissue types in two genetic AD mouse models under colonized or germ-free conditions, complemented shotgun metagenomics sequencing data (666 samples). Systems-level analyses 3xTg and 5xFAD mice reveal clusters dysregulated molecular classes across tissues including carnitines, bile acids, B vitamins, neurotransmitters. This signature, coupled with microbiome profiles, suggests increased oxidative stress via mitochondrial dysfunction. Molecular feature tracking tissueMASST, mass spectrometry search tool developed to bridge animal model findings human data, identifies microbially-modulated phenylacetyl-carnitine as positively associated aging cognitive impairment studies. With hundreds yet-to-be-characterized metabolites, this public resource its tools will aid future research the pathophysiology AD.

Language: Английский

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