Oral Cavity and Brain Cross-talk in Alzheimer's Disease

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Summary Although Alzheimer’s disease (AD) is an age-associated neurodegenerative disease, continuing evidence demonstrates pathophysiology outside of the brain. This suggests a more complex process of disease with systemic manifestations as well. Numerous studies now demonstrate that changes in the oral cavity have a relationship with AD. Human patients have elevated salivary Aβ concentrations and reported problems with saliva flow. In addition, periodontal disease, tooth loss, and overall poor oral health are all positive risk factors for AD. This suggests that AD and periodontal health may have a reciprocal relationship. Using two different transgenic mouse amyloidosis models of AD, APP/PS1 and AppNL-G-F mice, we verified not only Aβ secretion in saliva, but a unique disease-associated oral microbiome and enamel thinning and increased cavities compared to wild type controls. Based upon these findings and prior work by others, we hypothesize that that oral cavity changes are a peripheral manifestation of AD contributing to disease progression. We will continue using the AppNL-G-F mouse line to fully define oral health across age and disease stage in the first aim. In the second aim we will determine whether salivary secretion of Aβ is needed for the oral dysbiosis and decline in oral health in the AD line. In the third aim we will determine whether the oral dysbiosis is specifically responsible for the decline in oral health and brain presentation of disease in the mice. This study will define an innovative mechanism demonstrating that oral cavity dysbiosis and dysfunction is a characteristic of disease which also contributes to AD progression. We expect to find that salivary Aβ secretion contributes to oral dysbiosis and changing the oral microbiome is sufficient to ameliorate disease presentation in the brain. This will demonstrate a new bi-directional understanding of disease involving a mouth-brain axis.