ArticleJournal of Alzheimer's disease : JAD2021
Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer's Disease.
Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Systematic Review: Porphyromonas gingivalis Outer Membrane Vesicles From Pathogenesis to Therapeutic Implications.International dental journal · 2026Pooled it
- Periodontitis and Tooth Loss Are Associated With Higher Risks of Cognitive Disorders: A Systematic Umbrella Meta-Analysis.Clinical and experimental dental research · 2025Pooled it
- Dysbiotic shift in the oral microbiota of patients with Alzheimer's disease compared to their healthy life partners-a combinatorial approach and a paired study design.Alzheimer's research & therapy · 2026Article
- Deciphering macrophage molecular responses toFrontiers in microbiology · 2026Article
- The Role of Salivary Diagnostics in Early Detection of Systemic and Oral Diseases: A Comprehensive Review.Cureus · 2025Review
- Salivary lactoferrin levels in Down Syndrome: a case-control study.Brain, behavior, & immunity - health · 2025Article
- Oral microbiota and central nervous system diseases: A review.Neuroprotection (Chichester, England) · 2025Review
- Oral Health Status and Factors Associated with Oral Health in Patients with Alzheimer's Disease: A Matched Case-Control Observational Study.Journal of clinical medicine · 2025Article
- Porphyromonas gingivalis and Its Outer Membrane Vesicles Induce Neuroinflammation in Mice Through Distinct Mechanisms.Immunity, inflammation and disease · 2025Article
- Exploring the Link Between Periodontitis and Alzheimer's Disease-Could a Nanoparticulate Vaccine Break It?Pharmaceutics · 2025Review
- Alzheimer's Disease andLife (Basel, Switzerland) · 2025Review
- Membrane vesicles from Red Complex bacteria: key players in oral pathogenesis, immune disruption, systemic diseases, and therapeutic insights.Frontiers in oral health · 2025Review
- Oral bacteriophages and their potential as adjunctive treatments for periodontitis: a narrative review.Journal of oral microbiology · 2025Review
- Porphyromonas gingivalis outer membrane vesicles alter cortical neurons and Tau phosphorylation in the embryonic mouse brain.PloS one · 2025Article
- Proteomic analysis of P. gingivalis-Lipopolysaccharide induced neuroinflammation in SH-SY5Y and HMC3 cells.GeroScience · 2024Article
- Reduced Salivary Lactoferrin Levels in Early-Onset Alzheimer's Disease.Aging and disease · 2024Article
- Oral Microbially-Induced Small Extracellular Vesicles Cross the Blood-Brain Barrier.International journal of molecular sciences · 2024Article
- Hemophore-like proteins of the HmuY family in the oral and gut microbiome: unraveling the mystery of their evolution.Microbiology and molecular biology reviews : MMBR · 2024Review
- Ethanol extract from Astilbe chinensis inflorescence suppresses inflammation in macrophages and growth of oral pathogenic bacteria.PloS one · 2024Article
- Implication of salivary lactoferrin and periodontal-mediated infections in Alzheimer's disease.Neural regeneration research · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Porphyromonas gingivalis (Pg) is a primary oral pathogen in the widespread biofilm-induced "chronic" multi-systems inflammatory disease(s) including Alzheimer's disease (AD). It is possibly the only second identified unique example of a biological extremophile in the human body. Having a better understanding of the key microbiological and genetic mechanisms of its pathogenesis and disease induction are central to its future diagnosis, treatment, and possible prevention. The published literature around the role of Pg in AD highlights the bacteria's direct role within the brain to cause disease. The available evidence, although somewhat adopted, does not fully support this as the major process. There are alternative pathogenic/virulence features associated with Pg that have been overlooked and may better explain the pathogenic processes found in the "infection hypothesis" of AD. A better explanation is offered here for the discrepancy in the relatively low amounts of "Pg bacteria" residing in the brain compared to the rather florid amounts and broad distribution of one or more of its major bacterial protein toxins. Related to this, the "Gingipains Hypothesis", AD-related iron dyshomeostasis, and the early reduced salivary lactoferrin, along with the resurrection of the Cholinergic Hypothesis may now be integrated into one working model. The current paper suggests the highly evolved and developed Type IX secretory cargo system of Pg producing outer membrane vesicles may better explain the observed diseases. Thus it is hoped this paper can provide a unifying model for the sporadic form of AD and guide the direction of research, treatment, and possible prevention.
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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.