ArticleMolecular & cellular proteomics : MCP2025
Oral Microbiome-Derived Proteins in Brain Extracellular Vesicles Circulate and Tie to Specific Dysbiotic and Neuropathological Profiles in Age-Related Dementias.
Article in Molecular & cellular proteomics : MCP, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- The Oral-Gut-Brain Axis in Pediatric Populations: The Implications of Oral Dysbiosis for Systemic Inflammation and Neuroinflammation.Nutrients · 2026Review
- The Microbiota as a Potential Cause of Disease.Diseases (Basel, Switzerland) · 2026Review
- Review
- Brain and circulating EV proteome signatures in schizophrenia as prognostic markers for age-related dementia.Acta neuropathologica communications · 2026Article
- Stem cell extracellular vesicles for neuropsychiatric disorders and translation.Extracellular vesicles and circulating nucleic acids · 2026Review
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Authors and funding
19 authors.
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Abstract
The involvement of the oral microbiome (OM) in the pathophysiology of Alzheimer's disease and vascular dementia has been recognized epidemiologically, but the molecular mechanisms remain elusive. In this study, we uncovered the presence of OM-derived proteins (OMdPs) in brain extracellular vesicles (bEVs) from post-mortem Alzheimer's disease and vascular dementia subjects using unbiased metaproteomics. OMdP circulation in blood EVs was also confirmed in an independent cohort. Our findings also reveal that specific OMdPs are present in bEVs, with their levels varying with disease progression. Peptidome-wide correlation analyses further explored their exchange dynamics and composition within bEVs. In addition, we validated the ability of OM-derived EVs to cross the blood-brain barrier using a blood-brain barrier-on-a-chip model, confirming a potential route for bacterial-derived molecules to reach the central nervous system. Bioinformatics-driven interaction analyses indicated that OMdPs engage with key neuropathological proteins, including amyloid-beta and tau, suggesting a novel mechanism linking dysbiotic OM to dementia. These results provide new insights into the role of the OM in neurodegeneration and highlight OMdPs as potential biomarkers and therapeutic targets.
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