Evidence map›Paper›PMID 42362546›Full record

ArticleNature communications2026

Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology.

Vaibhav Vemuganti, Jea Woo Kang, Qijun Zhang, Eric R McGregor, James R Hilser, Ruben Aquino-Martinez, Sandra Harding, Joseph Lawrence Harpt, Katharina R Beck, Hailey Bussan and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Vaibhav Vemuganti *Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0009-0002-7353-9683
Jea Woo Kang *Wisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0003-1202-4432
Qijun ZhangDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-1003-7355
Eric R McGregorDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
James R HilserDivision of Cardiology, Department of Medicine, David Geffen School of Medicine of UCLA, Los Angeles, California, USA.ORCID http://orcid.org/0000-0001-5849-7839
Ruben Aquino-MartinezDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Sandra HardingWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Joseph Lawrence HarptDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Katharina R BeckWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Hailey BussanDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Jessamine F KuehnDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-2719-2474
Yuetiva DemingWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Rachel StuderWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Sterling C JohnsonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-8501-545X
Sanjay AsthanaWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-3298-6324
Henrik ZetterbergWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.ORCID http://orcid.org/0000-0002-1890-4193
Corinne D EngelmanDepartment of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0003-4750-5607
Hooman AllayeeDivision of Cardiology, Department of Medicine, David Geffen School of Medicine of UCLA, Los Angeles, California, USA.
Rozalyn M AndersonDepartment of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-0864-7998
Tyler K UllandWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Fredrik BäckhedWallenberg Laboratory, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden.
Barbara B BendlinWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. bbb@medicine.wisc.edu.ORCID http://orcid.org/0000-0002-0580-9875
Federico E ReyDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA. ferey@wisc.edu.ORCID http://orcid.org/0000-0002-0239-7780

Funding

Gut barrier function in Alzheimer's DiseaseR01AG070973 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, REY, FEDERICO E · 2021 to 2025
$3.9M
ß-hydroxybutyrate inhibition of pathology in Alzheimer's diseaseR01AG083883 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin, Federico E Rey · 2023 to 2026
$3.8M
CRCNS: Repurposing Transformers to Characterize Gut Microbiome & Aging Brain AxisR01AG092220 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin, Federico E Rey · 2024 to 2026
$1.1M
Genetic and Gut Microbial Regulation of Indole-3 Propionate in Metabolic DiseaseR01DK143650 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Hooman Allayee, Aldons Jake Lusis · 2026 to 2026
$779k
Exploring the role of Imidazole Propionate on Alzheimer’s Disease and Related DementiasR21AG089348 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, REY, FEDERICO E · 2024 to 2025
$408k
NIA NIH HHS R01 AG070973NIA NIH HHS R01 AG083883NIA NIH HHS R01 AG092220NIA NIH HHS R21 AG089348NIDDK NIH HHS R01 DK143650
6 · The paper itself

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.

Indexed as

Alzheimer DiseaseGastrointestinal MicrobiomeImidazolesPropionatesAgedAnimalsBiomarkersBrainFecesFemaleGlycogen Synthase Kinase 3 betaHumansMaleMiceMice, Inbred C57BLNeurons5-imidazolepropionic acidBiomarkersGlycogen Synthase Kinase 3 betaImidazolesPropionatestau Proteins

Identifiers

PMID42362546
PMCPMC13454616

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.