{
  "abstract": "The gut microbiome modulates metabolic and neurovascular processes implicated in Alzheimer's disease and related dementias (ADRD), but the underlying mechanisms remain unclear. Here, we identify the bacterial metabolite imidazole propionate (ImP) as a modifier of ADRD pathology. In a cohort of 1196 cognitively unimpaired adults, higher plasma ImP levels were associated with lower preclinical cognitive scores and biomarkers of ADRD, both cross-sectionally and longitudinally. Fecal metagenomic analysis linked putative ImP producers to ADRD phenotypes. Genome-wide integrative analysis revealed a locus on chromosome 12 associated with both plasma ImP levels and AD risk in humans, supporting a host genetic contribution to ImP regulation and a causal role of this metabolite in AD. In mice, chronic ImP administration exacerbated AD-like pathology. ImP impaired brain endothelial barrier and promoted tau hyperphosphorylation in primary neurons, an effect blocked by glycogen synthase kinase-3β inhibition. Together, this study links ImP to hallmarks of neurodegeneration and suggests that targeting ImP may represent a potential strategy to modify ADRD risk.",
  "abstract_shown": true,
  "affiliations": [
    "Cellular and Molecular Pathology Graduate Training Program, University of Wisconsin-Madison, Madison, WI, USA",
    "Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA",
    "Cellular and Molecular Pathology Graduate Training Program, University of Wisconsin-Madison",
    "Madison, WI, USA",
    "Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA",
    "Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison",
    "Department of Bacteriology, University of Wisconsin-Madison",
    "Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA",
    "Division of Cardiology, Department of Medicine, David Geffen School of Medicine of UCLA, Los Angeles, California, USA",
    "Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin",
    "Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden",
    "Centre for Brain Research, Indian Institute of Science; Bangalore, India",
    "Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital; Mölndal, Sweden",
    "Department of Neurodegenerative Disease, UCL Institute of Neurology; Queen Square, London, UK",
    "Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg; Mölndal, Sweden",
    "Hong Kong Center for Neurodegenerative Diseases; Inn, 6, oHK, Hong Kong, China",
    "UK Dementia Research Institute at UCL; London, UK",
    "Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison; Madison, WI, USA",
    "Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital",
    "Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg",
    "Hefei, P.R. China",
    "Mölndal, Sweden",
    "Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC",
    "Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University",
    "Department of Population Health Sciences, University of Wisconsin-Madison",
    "Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison",
    "Wisconsin Alzheimer's Institute, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA",
    "Kongens Lyngby, Denmark",
    "Microbiome Health Initiative and the National Food Institute, Technical University of Denmark",
    "Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Physiology; Gothenburg, Sweden",
    "Wallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg",
    "Centre for Brain Research, Indian Institute of Science, Bangalore, India",
    "Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden",
    "Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden",
    "Hong Kong Center for Neurodegenerative Diseases, Inn,6,oHK, Hong Kong, China",
    "UK Dementia Research Institute at UCL, London, UK",
    "Department of Medical Microbiology and Immunology, University of Wisconsin-Madison",
    "Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, P.R. China",
    "Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France",
    "Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Vaibhav Vemuganti",
      "orcid": "0009-0002-7353-9683"
    },
    {
      "affs": [
        4,
        3,
        5
      ],
      "name": "Jea Woo Kang",
      "orcid": "0000-0003-1202-4432"
    },
    {
      "affs": [
        1,
        6,
        3
      ],
      "name": "Qijun Zhang",
      "orcid": "0000-0002-1003-7355"
    },
    {
      "affs": [
        7,
        6,
        3
      ],
      "name": "Eric R. McGregor"
    },
    {
      "affs": [
        8,
        3,
        5
      ],
      "name": "James R. Hilser",
      "orcid": "0000-0001-5849-7839"
    },
    {
      "affs": [
        1,
        6,
        3
      ],
      "name": "Ruben Aquino-Martinez"
    },
    {
      "affs": [
        4,
        3,
        5
      ],
      "name": "Sandra Harding"
    },
    {
      "affs": [
        1,
        3,
        5,
        9
      ],
      "name": "Joseph Lawrence Harpt"
    },
    {
      "affs": [
        10,
        3,
        5,
        9
      ],
      "name": "Katharina R. Beck",
      "orcid": "0000-0001-9818-1265"
    },
    {
      "affs": [
        1,
        11,
        12,
        13,
        14,
        15,
        16,
        17
      ],
      "name": "Hailey Bussan"
    },
    {
      "affs": [
        1,
        18,
        19,
        20,
        21,
        22,
        23
      ],
      "name": "Jessamine F. Kuehn",
      "orcid": "0000-0002-2719-2474"
    },
    {
      "affs": [
        4,
        24,
        3
      ],
      "name": "Yuetiva Deming"
    },
    {
      "affs": [
        4,
        25,
        3
      ],
      "name": "Rachel Studer"
    },
    {
      "affs": [
        4,
        26,
        27,
        28,
        29,
        30
      ],
      "name": "Sterling C. Johnson",
      "orcid": "0000-0002-8501-545X"
    },
    {
      "affs": [
        4,
        26,
        3,
        5,
        9
      ],
      "name": "Sanjay Asthana",
      "orcid": "0000-0002-3298-6324"
    },
    {
      "affs": [
        31,
        32,
        13,
        33,
        34,
        35,
        4,
        36,
        3
      ],
      "name": "Henrik Zetterberg",
      "orcid": "0000-0003-3930-4354"
    },
    {
      "affs": [
        32,
        33,
        37,
        38
      ],
      "name": "Kaj Blennow",
      "orcid": "0000-0002-1890-4193"
    },
    {
      "affs": [
        39
      ],
      "name": "Corinne D. Engelman",
      "orcid": "0000-0003-4750-5607"
    },
    {
      "affs": [
        8
      ],
      "name": "Hooman Allayee"
    },
    {
      "affs": [
        7
      ],
      "name": "Rozalyn M. Anderson",
      "orcid": "0000-0002-0864-7998"
    },
    {
      "affs": [
        4
      ],
      "name": "Tyler Kent Ulland",
      "orcid": "0000-0002-6507-4989"
    },
    {
      "affs": [
        10
      ],
      "name": "Fredrik Bäckhed",
      "orcid": "0000-0002-4871-8818"
    },
    {
      "name": "Barbara B. Bendlin",
      "orcid": "0000-0002-0580-9875"
    },
    {
      "name": "Federico E. Rey",
      "orcid": "0000-0002-0239-7780"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9pqzzfvtwrb4t.bib",
  "cited_by": 7,
  "doi": "10.1038/s41467-026-74744-z",
  "fulltext_url": null,
  "id": "9pqzzfvtwrb4t",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-74744-z",
  "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": [
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      "2804|Alzheimer's disease research and treatments"
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  "pdf_url": null,
  "pmcid": "PMC12157550",
  "pmid": "40501659",
  "published": "2026-06-26",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/9pqzzfvtwrb4t.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T13:20:55Z",
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      "url": "https://doi.org/10.1038/s41467-026-74744-z"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Alzheimer's disease research and treatments",
      "subfield": "neuroscience"
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  ],
  "title": "Gut bacterial metabolite imidazole propionate potentiates Alzheimer’s disease pathology",
  "title_text": "Gut bacterial metabolite imidazole propionate potentiates Alzheimer’s disease pathology",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:48Z",
  "url": "https://research.draconitic.com/paper/9pqzzfvtwrb4t",
  "venue": "Nature Communications",
  "versions": []
}