Periodontitis Deteriorates Cognitive Function and Impairs Neurons and Glia in a Mouse Model of Alzheimer's Disease

Background: Although periodontitis is reportedly associated with increased cognitive decline in Alzheimer's disease, the mechanisms underlying this process remain unknown. Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) is an endotoxin associated with periodontal disease. Objective: We investigated the effect of periodontitis on learning capacity and memory of amyloid-beta protein precursor (A beta PP)/presenilin (PS1) transgenic mice along with the mechanisms underlying these effects. Methods: Mice were randomly assigned to three groups, namely A beta PP/PS1 (control), P.g-LPS Injection, and P.g-LPS Injection + Ligation. Mice from the P.g-LPS Injection group were injected with P.g-LPS in the periodontal tissue three times per week for 8 weeks, while mice from the P.g-LPS Injection + Ligation group were injected with P.g-LPS and subjected to ligation of the gingival sulcus of the maxillary second molar. Results: Expression of gingival proinflammatory cytokines as well as alveolar bone resorption in P.g-LPS-injected and ligatured mice was increased compared to that in control mice. Mice in the P.g-LPS Injection + Ligation group exhibited cognitive impairment and a significant reduction in the number of neurons. Glial cell activation in the experimental groups with significantly increased amyloid-beta (A beta) levels was more pronounced relative to the control group. Induction of periodontitis was concurrent with an increase in cyclooxygenase-2, inducible nitric oxide synthase, A beta PP, and beta-secretase 1 expression and a decrease in A disintegrin and metalloproteinase domain-containing protein 10 expression. Conclusion: These findings indicated that periodontitis exacerbated learning and memory impairment in A beta PP/PS1 mice and augmented A beta and neuroinflammatory responses. Our study provides a theoretical basis for risk prediction and early intervention of Alzheimer's disease and periodontitis.

Automated summary

The study found that periodontitis exacerbated learning and memory impairment in A beta PP/PS1 mice, leading to an increase in A beta and neuroinflammatory responses.