ArticleJournal of Alzheimer's disease : JAD2022
Trimethylamine N-Oxide Reduces Neurite Density and Plaque Intensity in a Murine Model of Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Association of trimethylamine oxide and its precursors with cognitive impairment: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- Article
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Select microbial metabolites promote tau aggregation in a murine tauopathy model.Nature communications · 2026Article
- Importance of Gut Microbiota Dysbiosis and Circadian Disruption-Associated Biomarkers in Emergence of Alzheimer's Disease.Molecular neurobiology · 2025Review
- The gut-brain axis in Alzheimer's disease: how gut microbiota modulate microglial function.Frontiers in aging · 2025Review
- Gut-brain axis and brain health: modulating neuroinflammation, cognitive decline, and neurodegeneration.3 Biotech · 2025Review
- Gut microbial metabolism in Alzheimer's disease and related dementias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Gut microbiome-derived metabolites in Alzheimer's disease: Regulation of immunity and potential for therapeutics.Immunological reviews · 2024Review
- From Gut Microbiota to Brain Waves: The Potential of the Microbiome and EEG as Biomarkers for Cognitive Impairment.International journal of molecular sciences · 2024Review
- Role of inflammatory cytokines and the gut microbiome in vascular dementia: insights from Mendelian randomization analysis.Frontiers in microbiology · 2024Article
- Machine Learning Algorithms Applied to Predict Autism Spectrum Disorder Based on Gut Microbiome Composition.Biomedicines · 2023Article
- Effect of a Vegan Diet on Alzheimer's Disease.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) is the most common aging-associated neurodegenerative disease; nevertheless, the etiology and progression of the disease is still incompletely understood. We have previously shown that the microbially-derived metabolite trimethylamine N-oxide (TMAO) is elevated in the cerebrospinal fluid (CSF) of individuals with cognitive impairment due to AD and positively correlates with increases in CSF biomarkers for tangle, plaque, and neuronal pathology.
objectiveWe assessed the direct impact of TMAO on AD progression.
methodsTo do so, transgenic 5XFAD mice were supplemented with TMAO for 12 weeks. Neurite density was assessed through quantitative brain microstructure imaging with neurite orientation dispersion and density imaging magnetic resonance imaging (MRI). Label-free, quantitative proteomics was performed on cortex lysates from TMAO-treated and untreated animals. Amyloid-β plaques, astrocytes, and microglia were assessed by fluorescent immunohistochemistry and synaptic protein expression was quantified via western blot.
resultsOral TMAO administration resulted in significantly reduced neurite density in several regions of the brain. Amyloid-β plaque mean intensity was reduced, while plaque count and size remained unaltered. Proteomics analysis revealed that TMAO treatment impacted the expression of 30 proteins (1.5-fold cut-off) in 5XFAD mice, including proteins known to influence neuronal health and amyloid-β precursor protein processing. TMAO treatment did not alter astrocyte and microglial response nor cortical synaptic protein expression.
conclusionThese data suggest that elevated plasma TMAO impacts AD pathology via reductions in neurite density.
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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.