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Record W4409958788 · doi:10.1101/2025.04.28.651123

A Multi-Organ Murine Metabolomics Atlas Reveals Molecular Dysregulations in Alzheimer’s Disease

2025· preprint· en· W4409958788 on OpenAlexfundno aff
Simone Zuffa, Celeste Allaband, Vincent Charron‐Lamoureux, Andrés Mauricio Caraballo‐Rodríguez, Abubaker Patan, Ipsita Mohanty, Julius Agongo, John W. Bostick, T. Jaymie Connerly, Taren Thron, Brittany Needam, Matheus de Castro Fonseca, Rodolfo A. Salido, Lauren Hansen, Helena M. Tubb, Jennifer Cao, Karel Kalecký, Teodoro Bottiglieri, Siamak MahmoudianDehkordi, Leyla Schimmel, Alexandra Kueider‐Paisley, Stewart F. Graham, Dionicio Siegel, Mingxun Wang, Rob Knight, Rima Kaddurah‐Daouk, Pieter C. Dorrestein, Sarkis K. Mazmanian

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolomics and Mass Spectrometry Studies
Canadian institutionsnot available
FundersNational Institute on AgingFonds de Recherche du Québec - Santé
KeywordsMetabolomicsAtlas (anatomy)DiseaseAlzheimer's diseaseComputational biologyNeuroscienceBiologyMedicineBioinformaticsPathologyAnatomy

Abstract

fetched live from OpenAlex

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 by shotgun metagenomics sequencing data (666 samples). Systems-level analyses of 3xTg and 5xFAD mice reveal clusters of dysregulated molecular classes across tissues including carnitines, bile acids, B vitamins, and neurotransmitters. This signature, coupled with microbiome profiles, suggests increased oxidative stress via mitochondrial dysfunction. Molecular feature tracking via tissueMASST, a mass spectrometry search tool we developed to bridge animal model findings with human data, identifies microbially-modulated phenylacetyl-carnitine as positively associated with aging and cognitive impairment across human AD studies. With hundreds of yet-to-be-characterized metabolites, this public resource and its associated tools will aid future research in the pathophysiology of AD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.250
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations13
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicMetabolomics and Mass Spectrometry StudiesFrench-language works237,207