ArticleJournal of Alzheimer's disease : JAD2020
Alzheimer's Disease-Like Neurodegeneration in Porphyromonas gingivalis Infected Neurons with Persistent Expression of Active Gingipains.
Article in Journal of Alzheimer's disease : JAD, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Gingipain inhibitors as an innovative therapy for periodontal and associated-systemic diseases: a systematic review.Clinical oral investigations · 2025Pooled it
- Mutagenesis and free energy calculations to optimize the ProRgpB inhibitor loop and identify variants with higher affinity forRSC advances · 2026Article
- The relationship betweenJournal of Alzheimer's disease : JAD · 2026Article
- From Periodontal Pocket to Systemic Diseases: Mechanistic Insights Into the Role of Porphyromonas gingivalis in Host Pathology.Journal of cellular and molecular medicine · 2026Review
- Red Complex Pathogens, Periodontal Dysbiosis and Periodontal Therapy in Alzheimer's Disease and Dementia.Journal of clinical medicine · 2026Review
- Prevalence and Risk Factors of Dementia Among Older People of Gelao Ethnicity in China: A National Cross-Sectional Study.CNS neuroscience & therapeutics · 2026Article
- Chronic periodontitis and systemic inflammation in the elderly: implications for neurodegeneration.Journal of neuroinflammation · 2026Review
- Different stages of Alzheimer's disease with periodontitis: clinical features and potential mechanisms involving gingipains, neuropathological biomarkers and neurological damage.Frontiers in aging neuroscience · 2026Article
- Coinfection ofFrontiers in immunology · 2026Article
- TLRs and NLRs modulate oral microbiome involvement in Alzheimer's disease.Metabolic brain disease · 2025Review
- Oral-Gut Microbiota Crosstalk and Epigenetic Targets in Metabolic and Neuropsychiatric Diseases.Nutrients · 2025Review
- Multi-Omics Insights into Gingivitis from a Clinical Trial: Understanding the Role of Bacterial and Host Factors.Microorganisms · 2025Article
- The Role of Oral and Gut Microbiota in Bone Health: Insights from Bacterial Extracellular Vesicles.Microorganisms · 2025Review
- Alzheimer's Disease and Oral Health from Clinical Challenges to Interdisciplinary Care: A Narrative Review.Journal of clinical medicine · 2025Review
- The role of the oral microbiome, host response, and periodontal disease treatment in Alzheimer's disease: A primer.Periodontology 2000 · 2025Review
- Reciprocal Interactions Between Periodontal Disease and Alzheimer's Disease: Implications for Mutual Triggering, Exacerbation, and Treatment Interventions-A Comprehensive Review of the Literature.Neurology international · 2025Review
- The Oral-Gut Microbiome-Brain Axis in Cognition.Microorganisms · 2025Review
- Alzheimer's Disease andLife (Basel, Switzerland) · 2025Review
- Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer's Disease Pathogenesis-From Gut Microbiota and Viruses to Brain Biofilms.Microorganisms · 2025Review
- Viable but non-cultivable state in oral microbiota: a critical review of an underexplored microbial survival strategy.Frontiers in cellular and infection microbiology · 2025Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPorphyromonas gingivalis (P. gingivalis) and its gingipain virulence factors have been identified as pathogenic effectors in Alzheimer's disease (AD). In a recent study we demonstrated the presence of gingipains in over 90% of postmortem AD brains, with gingipains localizing to the cytoplasm of neurons. However, infection of neurons by P. gingivalis has not been previously reported.
objectiveTo demonstrate intraneuronal P. gingivalis and gingipain expression in vitro after infecting neurons derived from human inducible pluripotent stem cells (iPSC) with P. gingivalis for 24, 48, and 72 h.
methodsInfection was characterized by transmission electron microscopy, confocal microscopy, and bacterial colony forming unit assays. Gingipain expression was monitored by immunofluorescence and RT-qPCR, and protease activity monitored with activity-based probes. Neurodegenerative endpoints were assessed by immunofluorescence, western blot, and ELISA.
resultsNeurons survived the initial infection and showed time dependent, infection induced cell death. P. gingivalis was found free in the cytoplasm or in lysosomes. Infected neurons displayed an accumulation of autophagic vacuoles and multivesicular bodies. Tau protein was strongly degraded, and phosphorylation increased at T231. Over time, the density of presynaptic boutons was decreased.
conclusionP. gingivalis can invade and persist in mature neurons. Infected neurons display signs of AD-like neuropathology including the accumulation of autophagic vacuoles and multivesicular bodies, cytoskeleton disruption, an increase in phospho-tau/tau ratio, and synapse loss. Infection of iPSC-derived mature neurons by P. gingivalis provides a novel model system to study the cellular mechanisms leading to AD and to investigate the potential of new therapeutic approaches.
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