|FLODEN, ANGELA - University Of North Dakota|
|SOHRABI, MONA - University Of North Dakota|
|NOOKALA, SUBA - University Of North Dakota|
|COMBS, COLIN - University Of North Dakota|
Submitted to: Current Alzheimer Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/24/2020
Publication Date: 2/22/2021
Citation: Floden, A.M., Sohrabi, M., Nookala, S., Cao, J.J., Combs, C.K. 2021. Salivary beta amyloid secretion and altered oral microbiome in mouse models of Alzheimer’s disease. Current Alzheimer Research. 17:1133-1144. https://doi.org/10.2174/1567205018666210119151952.
Interpretive Summary: Although Alzheimer’s disease (AD) is well-known for its to the brain, there is accumulating evidence that AD affects other areas as well. For example, the small protein, called beta amyloid, that accumulates in the brain can be found in other parts of the body. Recent studies indicate that the gut microbiome differs in individuals with AD compared to those who are healthy. In this study, we asked whether beta amyloid could be found in saliva during AD and whether the bacteria living in the mouth differ. Using different mouse models of AD, we verified that beta amyloid was present in saliva and that oral bacteria were different compared to healthy mice. These findings suggest that a test measuring the beta amyloid or bacterial types in the mouth might be useful for monitoring AD progression or diagnosis.
Technical Abstract: Background: Beta amyloid peptide containing plaque aggregations in the brain are a hallmark of Alzheimer’s Disease (AD). However, Beta amyloid is produced by cell types outside of the brain suggesting that the peptide may serve a broad physiologic purpose. Objective: Based upon our prior work documenting expression of beta amyloid precursor protein (APP) in intestinal epithelium we hypothesized that salivary epithelium might also express APP and be a source of beta amyloid. Methods: To begin testing this idea, we compared human age-matched control and AD salivary glands to C57BL/6 wild type, App(NL-G-F), and APP/PS1 mice. Results: Both male and female AD, App(NL-G-F), and APP/PS1 glands demonstrated robust APP and beta amyloid immunoreactivity. This correlated with increased levels of particularly beta amyloid 1-42 in stimulated saliva from female App(NL-G-F) mice. No significant differences in total volume were observed in any group. Correlating with the levels of beta amyloid change, App(NL-G-F) but not APP/PS1 mice demonstrated a significant difference in oral microbiome diversity compared to wild type mice. Male, but not female, APP/PS1 and App(NL-G-F) mice had significantly thinner molar enamel compared to their wild type counterparts. Conclusion: These data support the idea that the oral microbiome changes during AD and correlates with changes in salivary beta amyloid and oral health in a sex-selective fashion.