Peer-reviewedCC BYCell Reports
A multi-organ metabolomics atlas reveals molecular dysregulations in Alzheimer’s disease mouse models
14 affiliations
- 1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Collaborative Mass Spectrometry Innovation Center, University of California, San Diego, La Jolla, CA, USA
- 2Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA
- 3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA
- 4Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA
- 5Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
- 6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA
- 7Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX, USA
- 8Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
- 9Metabolomics Department, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA; Oakland University-William Beaumont School of Medicine, Rochester, MI, USA
- 10Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA
- 11Department of Computer Science and Engineering, University of California, Riverside, Riverside, CA, USA
- 12Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; Duke Institute of Brain Sciences, Duke University, Durham, NC, USA; Department of Medicine, Duke University, Durham, NC, USA. Electronic address: [email protected]
- 13Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA; Collaborative Mass Spectrometry Innovation Center, University of California, San Diego, La Jolla, CA, USA. Electronic address: [email protected]
- 14Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. Electronic address: [email protected]
Abstract
The etiology of Alzheimer's disease (AD) remains unclear but is likely driven by gene-environment interactions. We present a multi-organ untargeted metabolomics atlas (n = 2,271) paired with metagenomics data (n = 666) from two AD transgenic mouse models (3xTg and 5xFAD) under colonized and germ-free conditions. Systems-level analyses revealed clusters of dysregulated molecules across tissues, including carnitines, bile acids, B vitamins, neurotransmitters, and N-acyl lipids. Metabolic shifts were associated with the depletion of Akkermansia muciniphila and enrichment of Mucispirillum schaedleri in the 3xTg model. We identify previously unexplored carnitines linked to microbial metabolism of phenylalanine. Using tissueMASST-a mass spectrometry search tool we developed to translate animal-model findings into a human clinical context-we trace phenylacetyl-carnitine in human plasma and serum samples (n = 1,470) from independent cohorts, revealing associations with aging, cognitive impairment, and diminished memory performance. This public resource and associated tools will aid future research in AD etiology.
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BibTeX
@article{zuffa2026multiorgan,
title = {{A multi-organ metabolomics atlas reveals molecular dysregulations in Alzheimer’s disease mouse models}},
author = {Simone Zuffa and Celeste Allaband and Vincent Charron‐Lamoureux and Andrés Mauricio Caraballo‐Rodríguez and Abubaker Patan and Ipsita Mohanty and Julius Agongo and John W. Bostick and T. Jaymie Connerly and Taren Thron and Brittany Needam and Matheus de Castro Fonseca and Rodolfo Antonio Salido Benítez and Lauren Hansen and Helena M. Tubb and Jennifer Cao and Karel Kalecký and Teodoro Bottiglieri and Siamak MahmoudianDehkordi and Leyla Schimmel and Alexandra Kueider‐Paisley and Stewart F. Graham and Dionicio Siegel and M Y Wang and Rob D. Knight and Rima F Kaddurah-Daouk and Pieter C. Dorrestein and Sarkis K. Mazmanian},
journal = {Cell Reports},
year = {2026},
month = jun,
doi = {10.1016/j.celrep.2026.117499},
url = {https://doi.org/10.1016/j.celrep.2026.117499},
note = {CC BY},
}
RIS
TY - JOUR
TI - A multi-organ metabolomics atlas reveals molecular dysregulations in Alzheimer’s disease mouse models
AU - Simone Zuffa
AU - Celeste Allaband
AU - Vincent Charron‐Lamoureux
AU - Andrés Mauricio Caraballo‐Rodríguez
AU - Abubaker Patan
AU - Ipsita Mohanty
AU - Julius Agongo
AU - John W. Bostick
AU - T. Jaymie Connerly
AU - Taren Thron
AU - Brittany Needam
AU - Matheus de Castro Fonseca
AU - Rodolfo Antonio Salido Benítez
AU - Lauren Hansen
AU - Helena M. Tubb
AU - Jennifer Cao
AU - Karel Kalecký
AU - Teodoro Bottiglieri
AU - Siamak MahmoudianDehkordi
AU - Leyla Schimmel
AU - Alexandra Kueider‐Paisley
AU - Stewart F. Graham
AU - Dionicio Siegel
AU - M Y Wang
AU - Rob D. Knight
AU - Rima F Kaddurah-Daouk
AU - Pieter C. Dorrestein
AU - Sarkis K. Mazmanian
PY - 2026
DA - 2026/06/01
JO - Cell Reports
DO - 10.1016/j.celrep.2026.117499
UR - https://doi.org/10.1016/j.celrep.2026.117499
AB - The etiology of Alzheimer's disease (AD) remains unclear but is likely driven by gene-environment interactions. We present a multi-organ untargeted metabolomics atlas (n = 2,271) paired with metagenomics data (n = 666) from two AD transgenic mouse models (3xTg and 5xFAD) under colonized and germ-free conditions. Systems-level analyses revealed clusters of dysregulated molecules across tissues, including carnitines, bile acids, B vitamins, neurotransmitters, and N-acyl lipids. Metabolic shifts were associated with the depletion of Akkermansia muciniphila and enrichment of Mucispirillum schaedleri in the 3xTg model. We identify previously unexplored carnitines linked to microbial metabolism of phenylalanine. Using tissueMASST-a mass spectrometry search tool we developed to translate animal-model findings into a human clinical context-we trace phenylacetyl-carnitine in human plasma and serum samples (n = 1,470) from independent cohorts, revealing associations with aging, cognitive impairment, and diminished memory performance. This public resource and associated tools will aid future research in AD etiology.
SN - 2211-1247
SN - 2639-1856
ER -