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

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.