ArticleAlzheimer's research & therapy2018
The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer's disease.
Article in Alzheimer's research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 papers, 5 of them syntheses that pooled it.
What it found
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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.
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.
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Who cites it
250 citing papers in PubMed, 5 syntheses or guidelines pooled it, 446 citations in OpenAlex.
- Microbiota-derived metabolite signatures in Alzheimer's disease across the cognitive aging continuum: a human-focused systematic review and evidence-weighted knowledge graph.Frontiers in microbiology · 2026Pooled it
- Pooled it
- The effects of microbiome-targeted therapy on cognitive impairment and postoperative cognitive dysfunction-A systematic review.PloS one · 2023Pooled it
- Probiotics for Alzheimer's Disease: A Systematic Review.Nutrients · 2021Pooled it
- Pooled it
- Computerized cognitive training enhances cognitive function in Alzheimer's disease by downregulating Ruminococcus-TMAO pathway.Journal of translational medicine · 2025Trial
- Article
- Metabolic profile association with white matter hyperintensity in patients with mild cognitive impairment.IBRO neuroscience reports · 2026Article
- Gut-brain axis in Alzheimer's disease: neuroinflammatory mechanisms and immunopharmacological interventions.Inflammopharmacology · 2026Review
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- The microbiota-proteostasis axis: implications in neurodegenerative diseases.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Cognitive-Motor Dual Task Training Synergistically Improves Aging-related Cognitive Dysfunction By Reducing TMAO and Suppressing TXNIP/NLRP3 Pathway.Molecular neurobiology · 2026Article
- Review
- Modulating the Gut-Microbiota-Brain Axis in Alzheimer's Disease: Therapeutic Potential of Nutritional and Metabolic Factors.CNS neuroscience & therapeutics · 2026Review
- Select microbial metabolites promote tau aggregation in a murine tauopathy model.Nature communications · 2026Article
- Is Ergothioneine an Important Source of Plasma TrimethylamineAntioxidants (Basel, Switzerland) · 2026Article
- Gut bacterial metabolite imidazole propionate potentiates Alzheimer's disease pathology.Nature communications · 2026Article
- The complex of gut microbial metabolites and sex hormones in Alzheimer's disease.Seminars in immunopathology · 2026Review
- Elevated serum trimethylamine N-oxide (TMAO) and trimethyllysine in patients with amyotrophic lateral sclerosis (ALS): An exploratory case-control study.IBRO neuroscience reports · 2026Article
- Review
190 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundTrimethylamine N-oxide (TMAO), a small molecule produced by the metaorganismal metabolism of dietary choline, has been implicated in human disease pathogenesis, including known risk factors for Alzheimer's disease (AD), such as metabolic, cardiovascular, and cerebrovascular disease.
methodsIn this study, we tested whether TMAO is linked to AD by examining TMAO levels in cerebrospinal fluid (CSF) collected from a large sample (n = 410) of individuals with Alzheimer's clinical syndrome (n = 40), individuals with mild cognitive impairment (MCI) (n = 35), and cognitively-unimpaired individuals (n = 335). Linear regression analyses were used to determine differences in CSF TMAO between groups (controlling for age, sex, and APOE ε4 genotype), as well as to determine relationships between CSF TMAO and CSF biomarkers of AD (phosphorylated tau and beta-amyloid) and neuronal degeneration (total tau, neurogranin, and neurofilament light chain protein).
resultsCSF TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals, and elevated CSF TMAO is associated with biomarkers of AD pathology (phosphorylated tau and phosphorylated tau/Aβ
conclusionsThese findings provide additional insight into gut microbial involvement in AD and add to the growing understanding of the gut-brain axis.
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What OpenQuestion holds
Registered trials
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.