Experimental periodontitis induced by P. Gingivalis exacerbated cognitive impairment and tau pathology in 3xTg AD mice

Abstract

Aims: Periodontitis is a common health problem in elderly, which can induce chronic systemic inflammation. Our research team has been studying how systemic inflammation affects the brain immune responses, which can then affect progression of Alzheimer’s disease (AD). Therefore, our aim is to apply experimental model of periodontitis in AD mice and examine cognitive dysfunctions and neuropathology. Methods: Female 3xTg mice at 6 months were injected with heat-killed P. gingivalis bacteria into their buccal mucosa three times per week every other week for a total of 5 weeks. Open field, spontaneous Y maze and puzzle box test were used to assess the sickness behavior and cognitive functions. Following behavioral testing, the mandibular jaws were harvested and subjected to micro-CT scan. Hippocampal regions were harvested for biochemical analysis. Results: Bacterial-induced periodontitis led to significant loss of periodontal bone level and exacerbated impairment of short- and long-term memory in 3xTg mice. When examining the hippocampus regions for phosphorylated tau protein levels, bacterial-induced periodontitis led to significant increase in Tau396 expression in both the total lysate and the sarkosyl-insoluble fractions. Conclusions: As bone loss induced by bacterial infection led to increased tau pathology and worsened hippocampal memory functions. Future work will aim to elucidate the mechanism of how periodontal bone loss lead to the development of AD pathology. Acknowledgement: The study is supported by Health and Medical Research Fund (HMRF 04151216) to RCCC. RPHW is awarded by Hong Kong PhD Fellowship.