Inflammation is central to both Alzheimer’s disease (AD) and periodontal disease (PD) which are the two most prevalent diseases in aging population. Chronic infections increase the systemic inflammation and the risk of development and progression of the AD. PD is initiated by the microbiome of the oral cavity that results in local inflammation and alveolar bone destruction. PD is one of the major causes of tooth loss in adults. Chronic systemic inflammation induced by PD is a risk factor for stroke, cardiovascular diseases, diabetes complications, rheumatoid arthritis, and preterm birth. Cross-sectional human studies suggest an association between AD and PD. Tooth loss in the elderly has been linked to cognitive decline and to AD. Recent studies demonstrate that the patients with PD have increased amyloid accumulation in brain. While epidemiological studies suggest PD may be a risk factor for AD, both conditions are multifactorial and share many of the same lifestyle factors (eg., tobacco smoking, low education). Our recent interest in the association of PD and AD resulted in the novel finding that Alzheimer mice have significant alveolar bone loss compared to wild-type littermates. This novel data if confirmed in other models of AD indicate the relationship between the AD and PD is bidirectional in that AD increases the PD and bone loss while increased PD creates a greater risk for AD associated pathology in the brain. We hypothesize that the association between PD and AD is bidirectional such that AD leads to periodontal tissue destruction and bone loss and that PD exacerbates the AD-associated pathological changes and neuroin- flammation and that systemic inflammation is central to this bidirectional association. We also hypothesize that the resolution of inflammation will restore homeostasis. We will use an experimental model of PD and transgenic mouse models of AD to find answers if (1) AD changes the periodontal microbiome that will lead to PD around the teeth, (2) if PD is a risk factor for the AD and (3) if the link between AD and PD is a failure of resolution of inflammation. We will build on our previous work where we showed that specialized mediators of resolution of inflammation (SPMs; e.g., lipoxins and resolvins) prevent and reverse the effects of inflammation and regenerate lost bone in PD when topically applied. We have also generated recent data that the SPMs prevented the neu- roinflammation and AD-associated pathologic changes restoring the brain health in Alzheimer mice. We will measure periodontal bone loss, neuroinflammatory markers, AD-related pathological changes, sys- temic markers of inflammation, and changes in oral microbiome. Immunohistochemistry, biochemistry, magnetic resonance spectroscopy (MRS), next-generation sequencing techniques and behavior tests will be employed in a multi-center setting to understand the mechanistic link between PD and AD and the resolution of inflammation as a potential therapeutic target.

Since aging is the main risk factor for developing both Alzheimer’s disease (AD) and periodontal disease (PD), it is possible that both may be associated by inflammation. Studying the activation and resolution of the inflammatory outcomes of AD and PD and dissecting the impact of aging will allow elucidation of the directionality of the link between both conditions and generate new therapeutic targets.