Induced Periodontitis in 3xTG Mice Increases Inflammation and Synaptic Degradation

Objectives: Alzheimer’s disease (AD) is the most common form of dementia in aging adults. Studies suggest that inflammation plays a key role in AD progression but little is known about the signaling pathways driving this. Periodontal disease (PD) is an aging disease in which chronic inflammation leads to bone and tooth loss in 20-50% of the global population. Several studies have found a positive correlation between AD and PD, but the mechanisms underlying their relationship remain unclear. Our objective was to test the hypothesis that inflammation associated with periodontitis could exacerbate AD progression and that the AD predisposition may similarly exacerbate periodontitis symptoms.
Methods: We induced periodontitis in transgenic AD (3xTg-AD) and WT mice with a silk ligature tied around the right second maxillary molar. We assessed bone loss with in vivo microcomputed tomography on days 0, 7 and 14. Levels of hippocampal inflammatory cytokines and neuronal receptors were measured using RT-PCR.
Results: WT and AD mice showed no differences in bone loss at 14 days. The non-ligature side showed minimal bone loss in both genotypes. qPCR data indicated an increase in inflammatory cytokine gene expression in the hippocampus of AD mice as compared to WT mice. There was also a significant decrease in gene expression of glutamate receptors and synaptic elements in the AD hippocampus after ligature placement.
Conclusions: PD-evoked bone loss in AD mice led to exaggerated hippocampal neuroinflammation and synaptic dysregulation. Studies are currently underway to assess behavioral modifications in AD mice with induced PD to provide a thorough characterization of how oral inflammation may lead to neuronal degradation. Future studies are planned to determine the mechanism that links PD with AD and other neurodegenerative diseases.