Connection Between Periodontitis and Alzheimer’s Disease: Possible Roles of Microglia and Leptomeningeal Cells

Abstract

Abstract. Neuroinflammation, inflammation of the brain, is strongly implicated in Alzheimer's disease (AD), which can be enhanced by systemic inflammation. Therefore, the initiation and progression of AD are affected by systemic diseases such as cardiovascular disease and diabetes. This concept suggests a possible link between periodontitis and AD because periodontitis is a peripheral, chronic infection that elicits a significant systemic inflammatory response. There is now growing clinical evidence that chronic periodontitis is closely linked to the initiation and progression of AD. Recent studies have suggested that leptomeningeal cells play an important role in transducing systemic inflammatory signals to the brain-resident microglia, which in turn initiate neuroinflammation. Furthermore, it is apparent that senescent-type microglia respond in an exaggerated manner to systemic inflammation. It is estimated that a high percentage of adults are suffering from periodontitis, and the prevalence of periodontitis increases with age. Therefore, chronic periodontitis can be a significant source of covert systemic inflammation within the general population. The present review article highlights our current understanding of the link between periodontitis and AD.

Periodontitis, periodontal inflammation, and mild cognitive impairment: A 5‐year cohort study

“…The observed associations between periodontitis and cognitive impairment appear to be biologically plausible. It has been suggested that sites of periodontal infection could be significant sources of inflammatory mediators and bacterial components, which may enter the central nervous system and cause neuronal damage . Although the evidence supporting the potential association between periodontitis and cognitive impairment is increasing, the results from previous studies are not consistent with those from several studies that did not find any significant association between periodontitis and cognitive impairment.…”

“…16 These inflammatory mediators and bacterial components may activate brain-resident microglia to evoke neuroinflammation, which ultimately contributes to cognitive impairment. 17 This theory is partly supported by a study that demonstrated the presence of LPS from Porphyromonas gingivalis in the 12-h postmortem brain tissue samples from Alzheimer's disease cases. 18 Second, periodontitis is reported to be associated with endothelial dysfunction, 19 which plays a role in the pathogenesis of vascular cognitive impairment.…”

“…Additionally, periodontal bacteria and their components, such as lipopolysaccharide (LPS), can enter the systemic circulation in patients with periodontitis . These inflammatory mediators and bacterial components may activate brain‐resident microglia to evoke neuroinflammation, which ultimately contributes to cognitive impairment . This theory is partly supported by a study that demonstrated the presence of LPS from Porphyromonas gingivalis in the 12‐h postmortem brain tissue samples from Alzheimer's disease cases .…”

Is Periodontal Disease Associated with Alzheimer's Disease? A Systematic Review with Meta-Analysis

“…Despite the existence of numerous narrative reviews [8,9,[13][14][15][16] , the use of subjective and non-standardized methods may have led to bias [17] . To the best of our knowledge, no previous systematic approach to this emerging topic can be found in the literature.…”

The downward spiral of periodontitis and diabetes in Alzheimer׳s disease: Extending healthy life expectancy through oral health

“…Development of treatments that delay the onset of AD by five years is estimated to potentially reduce the number of AD patients by half. Recently, considerable attention has been focused on lifestyle related diseases, including diabetes [1] and periodontitis [2][3][4][5], as exacerbating factors for AD. Periodontitis is also a risk factor for diabetes, and several recent clinical studies have demonstrated that periodontal treatment using antibiotics has beneficial effects on glycemic control for patients with type 2 diabetes [6].…”