{ "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.", "abstract_shown": true, "affiliations": [ "Skaggs 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", "Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA", "Division 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", "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA", "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA", "Division 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", "Center of Metabolomics, Institute of Metabolic Disease, Baylor Scott & White Research Institute, Dallas, TX, USA", "Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA", "Metabolomics Department, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA; Oakland University-William Beaumont School of Medicine, Rochester, MI, USA", "Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA", "Department of Computer Science and Engineering, University of California, Riverside, Riverside, CA, USA", "Department 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: rima.kaddurahdaouk@duke.edu", "Skaggs 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: pdorrestein@health.ucsd.edu", "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA. Electronic address: sarkis@caltech.edu" ], "article_type": null, "arxiv": null, "author_total": 28, "authors": [ { "affs": [ 0 ], "name": "Simone Zuffa", "orcid": "0000-0001-7237-3402" }, { "affs": [ 1 ], "name": "Celeste Allaband", "orcid": "0000-0003-1832-4858" }, { "affs": [ 0 ], "name": "Vincent Charron‐Lamoureux", "orcid": "0000-0001-9440-7036" }, { "affs": [ 0 ], "name": "Andrés Mauricio Caraballo‐Rodríguez", "orcid": "0000-0001-5499-2728" }, { "affs": [ 0 ], "name": "Abubaker Patan", "orcid": "0000-0003-1415-7829" }, { "affs": [ 0 ], "name": "Ipsita Mohanty", "orcid": "0000-0001-5311-6443" }, { "affs": [ 0 ], "name": "Julius Agongo", "orcid": "0009-0002-0115-1997" }, { "affs": [ 2 ], "name": "John W. Bostick", "orcid": "0000-0001-8925-2447" }, { "affs": [ 3 ], "name": "T. Jaymie Connerly", "orcid": "0009-0007-4124-051X" }, { "affs": [ 4 ], "name": "Taren Thron", "orcid": "0000-0001-9577-2617" }, { "affs": [ 5 ], "name": "Brittany Needam" }, { "affs": [ 4 ], "name": "Matheus de Castro Fonseca", "orcid": "0000-0001-9048-9775" }, { "affs": [ 1 ], "name": "Rodolfo Antonio Salido Benítez" }, { "affs": [ 1 ], "name": "Lauren Hansen" }, { "affs": [ 1 ], "name": "Helena M. Tubb", "orcid": "0000-0002-7637-5090" }, { "affs": [ 1 ], "name": "Jennifer Cao" }, { "affs": [ 6 ], "name": "Karel Kalecký", "orcid": "0000-0002-4212-6811" }, { "affs": [ 6 ], "name": "Teodoro Bottiglieri" }, { "affs": [ 7 ], "name": "Siamak MahmoudianDehkordi", "orcid": "0000-0002-6843-1718" }, { "affs": [ 7 ], "name": "Leyla Schimmel", "orcid": "0009-0005-3546-9612" }, { "affs": [ 7 ], "name": "Alexandra Kueider‐Paisley", "orcid": "0000-0001-7132-5003" }, { "affs": [ 8 ], "name": "Stewart F. Graham" }, { "affs": [ 9 ], "name": "Dionicio Siegel" }, { "affs": [ 10 ], "name": "M Y Wang" }, { "name": "Rob D. Knight", "orcid": "0000-0002-0975-9019" }, { "affs": [ 11 ], "name": "Rima F Kaddurah-Daouk", "orcid": "0000-0003-1858-5732" }, { "affs": [ 12 ], "name": "Pieter C. Dorrestein", "orcid": "0000-0002-3003-1030" }, { "affs": [ 13 ], "name": "Sarkis K. Mazmanian", "orcid": "0000-0003-2713-1513" } ], "bibtex": "https://research.draconitic.com/paper/2pex2v8a4dcn7.bib", "cited_by": 18, "doi": "10.1016/j.celrep.2026.117499", "fulltext_url": null, "id": "2pex2v8a4dcn7", "issns": [ "2211-1247", "2639-1856" ], "landing_url": "https://doi.org/10.1016/j.celrep.2026.117499", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "1312|Metabolomics and Mass Spectrometry Studies" ] ], "openalex": "W7165004807", "pdf_url": null, "pmcid": null, "pmid": "42308105", "published": "2026-06-01", "publisher": "Cell Press", "ris": "https://research.draconitic.com/paper/2pex2v8a4dcn7.ris", "sources": [ { "first_seen": "2026-11-04T13:21:05Z", "native_id": "W7165004807", "source": "openalex", "url": "https://doi.org/10.1016/j.celrep.2026.117499" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|Metabolomics and Mass Spectrometry Studies", "subfield": "molecular-biology" } ], "title": "A multi-organ metabolomics atlas reveals molecular dysregulations in Alzheimer’s disease mouse models", "title_text": "A multi-organ metabolomics atlas reveals molecular dysregulations in Alzheimer’s disease mouse models", "type": "peer-reviewed", "updated_at": "2026-11-05T13:20:46Z", "url": "https://research.draconitic.com/paper/2pex2v8a4dcn7", "venue": "Cell Reports", "versions": [] }