The impact of bacterial-induced periodontitis on experimental mouse model of Alzheimer’s disease

Abstract

Background: Alzheimer’s disease (AD) is the most common form of dementia characterized by the presence of amyloid plaques, neurofibrillary tangles and the activation of the brain immune system. Studies from the public health have shown that activation of the immune cells in the periphery can lead to neuroimmune responses, which can initiate or perpetuate neurodegenerative brain changes that underlie cognitive impairment. One of the common sources of chronic systemic inflammation is periodontitis, which is an inflammatory disease that destroys gums and teeth. We hypothesize that periodontal bone loss due to periodontitis gums may intensify the neuroimmune responses in AD and exacerbate the disease conditions. Methods: Female 3xTg mice at 6 months old 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 to establish periodontitis. 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 for Micro-CT scan. Different brain regions were harvested for biochemical analysis. Results: Bacterial-induced periodontitis led to a significant loss of periodontal bone level. When assessing the short-term memory using the spontaneous Y maze, bacterial-induced periodontitis induced and exacerbated impairment of short-term memory in AD mice. In addition, it induced and exacerbated impairment of long-term memory in 3xTg mice. Bacterial-induced periodontitis also led to significant increase in Tau396 expression in both the hippocampal total lysate and the sarkosyl-insoluble fractions. This was also confirmed by the immunostaining results. Conclusions: Taken together, bacterial-induced periodontitis led to periodontal bone loss, induced and exacerbated both short and long-term memory in 3xTg AD mice. Through biochemical analysis, bacterial-induced periodontitis also led to increased Tau396 expression levels in the hippocampus regions of 3xTg mice. 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.