Oral-Systemic Links: A Narrative Review of the Role of Periodontitis in Alzheimer’s Disease Development

Alzheimer’s disease (AD) and periodontitis are prevalent chronic conditions that disproportionately affect aging populations and pose substantial public health challenges worldwide. Increasing evidence suggests a potential association between these two diseases, with chronic oral infection and systemic inflammation emerging as key linking mechanisms. Periodontitis is characterized by a dysbiotic oral microbiome and persistent inflammatory responses that can lead to the dissemination of periodontal pathogens and their virulence factors into the systemic circulation. Notably, some studies have reported the detection of pathogens such as Porphyromonas gingivalis and their toxic products in the brains of individuals with AD, implicating a possible role in neuroinflammation and neurodegeneration. However, it should be clarified that detection does not establish causation. This narrative review aims to synthesize the existing evidence from animal studies exploring the link between periodontitis and AD and its related mechanisms, including neuroinflammation, amyloid and tau pathology, blood-brain barrier dysfunction, and systemic interactions. The electronic search in PubMed yielded 585 results. We focused on the past 10 years, thus removing 114 results. A total of 471 studies remained. Of the 471 articles reviewed, 239 studies were excluded based on their titles, abstracts, publication types, and topics because of inappropriate study designs (i.e., designs other than cross-sectional or animal studies). A total of 232 studies were further investigated. In this review, the analysis focused exclusively on animal studies, and the full texts were assessed against predefined eligibility criteria focusing on study design, animal model, periodontal exposure, and AD-related outcomes. Studies that met all inclusion criteria were included, whereas articles with inappropriate study designs or irrelevant outcomes were excluded. After full-text screening, 101 studies remained. Preclinical (animal) evidence supported plausible mechanistic links between periodontitis and AD. Furthermore, oral pathogens appear to mediate this ongoing neuroinflammation.