Salivary Aβ Secretion and Altered Oral Microbiome in Mouse Models of AD

Background: Beta amyloid (A beta) peptide containing plaque aggregations in the brain are a hallmark of Alzheimer's Disease (AD). However, A beta 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 amyloid beta precursor protein (APP) in intestinal epithelium we hypothesized that salivary epithelium might also express APP and be a source of A beta. 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 A beta immunoreactivity. Female App(NL-G-F) mice had significantly higher levels of pilocarpine stimulated A beta 1-42 compared to both wild type and APP/PS1 mice. No differences in male salivary A beta levels were detected. No significant differences in total pilocarpine stimulated saliva volumes were observed in any group. Both male and female App(NL-G-F) but not APP/PS1 mice demonstrated significant differences in oral microbiome phylum and genus abundance 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 oral microbiome changes exist during AD in addition to changes in salivary A beta and oral health.