The relationship between oral and systemic health has been recognized for over a century, beginning with the early “focal infection theory,” which proposed that chronic oral infections could contribute to systemic disease through the spread of pathogens in the bloodstream (Lowe, 1925). While this concept was initially controversial, growing evidence has supported links between oral health and conditions such as cardiovascular disease, and more recently, attention has shifted toward potential connections with neurodegenerative disorders, including Alzheimer’s disease (AD) (Nery et al., 1987).

Periodontitis is a highly prevalent chronic inflammatory disease characterized by bacterial infection of the supporting structures of the teeth. It is driven by complex microbial biofilms, including pathogens such as Porphyromonas gingivalis, which produce virulence factors that trigger strong host immune responses (Mehrotra & Singh, 2023). These responses lead to sustained inflammation, tissue destruction, and systemic dissemination of inflammatory mediators. Notably, components such as lipopolysaccharide (LPS) and gingipains produced by P. gingivalis have been shown to promote inflammatory signaling and may influence biological barriers, including the blood–brain barrier (Darveau et al., 2004; How et al., 2016; Lei et al., 2023; Li & Collyer, 2011; Sabbagh & Decourt, 2022).

Alzheimer’s disease, the most common form of dementia, is characterized by progressive cognitive decline and neuropathological hallmarks including amyloid-β (Aβ) plaque accumulation and chronic neuroinflammation (Abdulkhaliq et al., 2026; National Institute of Health, 2025). The formation of Aβ plaques triggers activation of microglia and astrocytes, leading to the release of pro-inflammatory cytokines and reactive oxygen species that contribute to neuronal damage (Heneka et al., 2025; Latz et al., 2013). Increasing evidence suggests that neuroinflammation is not only a consequence of disease progression but may also play a central role in driving amyloid pathology and neurodegeneration.    

Emerging epidemiological studies have identified associations between periodontitis and cognitive decline, suggesting that individuals with chronic periodontal disease may have an increased risk of developing Alzheimer’s disease (Eke et al., 2018; Gil-Montoya et al., 2017). Mechanistic research further supports this link, proposing that systemic inflammation, microbial translocation, and blood–brain barrier disruption may connect oral infection to neurodegenerative processes. However, despite growing biological plausibility, the strength and nature of this relationship remain uncertain, as many studies are limited by confounding variables, reverse causality, and a lack of direct experimental evidence in human populations.
Given these gaps, further investigation is needed to clarify how periodontal disease may influence key pathological features of Alzheimer’s disease. Therefore, the purpose of this study was to examine whether individuals with periodontitis exhibit increased neuroinflammation and amyloid burden compared to healthy controls using a simulated dataset.

It was hypothesized that the periodontitis group would demonstrate significantly higher levels of both neuroinflammation and amyloid burden, consistent with proposed inflammatory mechanisms linking oral health and neurodegeneration.