Ochoa KL, Heredia AG, Piedra CC, Arias RJ, Ortiz BJ, Dominguez-Gortaire JA. Association between Alzheimer's disease and Porphyromonas gingivalis products in murine models: A systematic review. World J Biol Chem 2025; 16(4): 111156 [DOI: 10.4331/wjbc.v16.i4.111156]
Corresponding Author of This Article
Jose A Dominguez-Gortaire, Professor, Facultad de Ciencias Biológicas, Universidad Central del Ecuador, Av. Yaguachi y Numa Pompillo, Quito 170403, Pichincha, Ecuador. jadominguezg@uce.edu.ec
Research Domain of This Article
Neurosciences
Article-Type of This Article
Systematic Reviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Biol Chem. Dec 5, 2025; 16(4): 111156 Published online Dec 5, 2025. doi: 10.4331/wjbc.v16.i4.111156
Association between Alzheimer's disease and Porphyromonas gingivalis products in murine models: A systematic review
Karen L Ochoa, Amy G Heredia, Camila C Piedra, Reymonth J Arias, Bengy J Ortiz, Jose A Dominguez-Gortaire
Karen L Ochoa, Amy G Heredia, Camila C Piedra, Reymonth J Arias, Bengy J Ortiz, Jose A Dominguez-Gortaire, Facultad de Ciencias Biológicas, Universidad Central del Ecuador, Quito 170403, Pichincha, Ecuador
Jose A Dominguez-Gortaire, Facultad de informática, Universidade de Coruña, A Coruna 15008, Galicia, Spain
Jose A Dominguez-Gortaire, Facultad de Odontología, University of Ecuador, Quito 170902, Ecuador
Author contributions: Ochoa KL contributed to conceptualization, methodology, formal analysis, data curation, writing–original draft; Heredia AG contributed to investigation, resources, data curation, writing–review and editing; Piedra CC contributed to investigation, validation, visualization, writing–review and editing; Arias RJ contributed to software, data curation, formal analysis, figure preparation; Ortiz BJ contributed to methodology, supervision, validation, writing–review and editing; Dominguez-Gortaire JA contributed to conceptualization, supervision, project administration, writing–original draft, final approval of the version to be published.
Conflict-of-interest statement: The authors declare that they have no commercial or financial relationships that could be construed as a potential conflict of interest. No competing interests exist regarding the publication of this manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jose A Dominguez-Gortaire, Professor, Facultad de Ciencias Biológicas, Universidad Central del Ecuador, Av. Yaguachi y Numa Pompillo, Quito 170403, Pichincha, Ecuador. jadominguezg@uce.edu.ec
Received: June 24, 2025 Revised: July 11, 2025 Accepted: October 22, 2025 Published online: December 5, 2025 Processing time: 163 Days and 13.4 Hours
Abstract
BACKGROUND
Alzheimer's disease is a neurodegenerative dementia characterized by accumulation of β-amyloid plaques, tau hyperphosphorylation, and neuroinflammation. Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration, particularly the involvement of Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontitis. Experimental mouse models have been used to explore how P. gingivalis products contribute to neuroinflammatory and degenerative processes. However, a comprehensive synthesis of these findings is lacking. This systematic review evaluates the role of P. gingivalis-derived factors in triggering Alzheimer's-like pathology, with an emphasis on bacterial products and host immune responses. We hypothesize that P. gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.
AIM
To link gingival P. gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.
METHODS
This systematic review followed the 2020 PRISMA guidelines. A comprehensive search was conducted in five databases (PubMed, Scopus, ScienceDirect, Sage, SpringerLink) for original studies between 2014 and 2024. Studies included mouse models to evaluate the effect of P. gingivalis or its products on Alzheimer's-like pathologies. Exclusion criteria were in vitro, human, or review studies. Twenty-three studies met the inclusion criteria. Bacterial components and activated host factors were extracted, categorized, and analyzed using narrative synthesis and descriptive statistics.
RESULTS
In 24 studies, lipopolysaccharides (54.84%) and gingipains (25.81%) were the most frequently reported P. gingivalis products. These factors activated toll-like receptors (TLR2/TLR4), microglia, and astrocytes, increasing levels of interleukin 1 beta, tumor necrosis factor-alpha, and other proinflammatory cytokines. The host response included β-amyloid accumulation, Tau hyperphosphorylation, and changes in blood-brain barrier permeability. Glial cells were the most frequently mentioned host factors (n = 15), followed by proteins (n = 13) and cytokines (n = 11). These interactions promoted cognitive impairment, synaptic dysfunction, and neurodegeneration in mouse models, supporting a role for P. gingivalis in Alzheimer's-like pathology.
CONCLUSION
P. gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models, supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
Core Tip: This review shows the role of Porphyromonas gingivalis (P. gingivalis)-derived products in Alzheimer's disease-like pathology in murine models. Lipopolysaccharides and gingipains were the most implicated bacterial factors, activating glial cells and proinflammatory pathways. These interactions resulted in β-amyloid accumulation, tau hyperphosphorylation, and cognitive impairment. Our analysis highlights the importance of chronic oral infection in the progression of Alzheimer's disease and supports P. gingivalis treatment as a potential preventive strategy.
