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Relationship of Porphyromonas gingivalis and Alzheimer’s disease: a systematic review of pre-clinical studies

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Abstract

Objectives

This study aimed to analyze the following PICO question: Are animals infected with Porphyromonas gingivalis (P. gingivalis) or bacterial lipopolysaccharide (Pg-LPS) more affected by neurodegeneration, similar to the pathogenesis generated by Alzheimer’s disease (AD), compared with non-infected animals?

Methods

Databases PubMed, Lilacs, SciELO, Science Direct, Scopus, Web of Science, and Cochrane were searched for pre-clinical in vivo studies in which mice were infected with P. gingivalis or received Pg-LPS, in order to assess the brain tissue and cognitive impairment. No limit for date or publication language was imposed and this study was registered at the International Prospective Register of Systematic Reviews (PROSPERO), with nine articles included. Syrcle’s protocol was used to evaluate bias in the selected studies.

Results

Nine articles were included. Infection by P. gingivalis or the administration of Pg-LPS increased the production of the inflammatory mediators, TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), and IL-1β (interleukin-1beta), augmented Aβ (amyloid beta) production, and activated the complement system, causing inflammation, brain tissue degeneration, and cognitive impairment, consistent with the damage in AD.

Conclusions

Infection by P. gingivalis and Pg-LPS administration appears to be in relation with the pathogenesis of AD by activating the complement cascade, increasing Aβ production and augmenting pro-inflammatory cytokine expression, causing age-dependent brain inflammation, neuroinflammation, and neurodegeneration.

Clinical relevance

Taking into account the importance of holistic treatment in the dental office, this study focuses on identifying highly prevalent oral diseases, such as periodontal disease, as risk factors for the aggravation of degenerative diseases in the elderly population.

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Funding

This work was supported by the Post-graduate Program in Dental Sciences, Federal University of Rio Grande do Norte (Brazil), and also by the Coordination for the Improvement of Higher-Level Personnel (CAPES/Brazil).

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Authors and Affiliations

  1. Department of Dentistry, Federal University of Rio Grande do Norte, Av. Sen. Salgado Filho, 1787 - Lagoa Nova, Natal, RN, 59056-000, Brazil

    Moan Jéfter Fernandes Costa, Isabela Dantas Torres de Araújo, Luana da Rocha Alves, Romerito Lins da Silva, Patricia dos Santos Calderon, Boniek Castillo Dutra Borges, Ana Rafaela Luz de Aquino Martins, Bruno Cesar de Vasconcelos Gurgel & Ruthineia Diogenes Alves Uchoa Lins

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  1. Moan Jéfter Fernandes Costa
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Correspondence to Moan Jéfter Fernandes Costa.

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Ethical approval

This work follows the entire protocol prepared by PRISMA for the elaboration of systematic reviews. Since the study was secondary data and did not involve humans, it did not require submission to an ethics committee. Nevertheless, all authors declare that they followed a well elaborated protocol to minimize conflicts or possible biases in the elaboration of the manuscript.

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No informed consent was required for this type of study.

Conflict of interest

All the authors involved in the elaboration of this manuscript declare there is no conflict of interest, be it ethical, moral or financial, with any of the information or magazines cited in the elaboration of this manuscript. Moan Jéfter Fernandes Costa declares that it knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Isabela Dantas Torres de Araújo declares that she knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Luana da Rocha Alves declares that she is aware of all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Romerito Lins da Silva declares that he knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Patricia dos Santos Calderon declares that she knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Boniek Castillo Dutra Borges declares that he knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Ana Rafaela Luz de Aquino Martins declares that she knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Bruno Cesar de Vasconcelos Gurgel declares that he knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest. Ruthineia Diogenes Alves Uchoa Lins declares that she knows all the steps taken, has actively participated in the production of the manuscript, and has no conflict of interest.

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Costa, M.J.F., de Araújo, I.D.T., da Rocha Alves, L. et al. Relationship of Porphyromonas gingivalis and Alzheimer’s disease: a systematic review of pre-clinical studies. Clin Oral Invest 25, 797–806 (2021). https://doi.org/10.1007/s00784-020-03764-w

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