Abstract

Background: Beta amyloid (Aβ) peptide containing plaque aggregations in the brain are a hallmark of Alzheimer’s Disease (AD). However, Aβ 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 β precursor protein (APP) in intestinal epithelium we hypothesized that salivary epithelium might also express APP and be a source of Aβ.

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 Aβ immunoreactivity. Female App^NL-G-F mice had significantly higher levels of pilocarpine stimulated Aβ 1-42 compared to both wild type and APP/PS1 mice. No differences in male salivary Aβ 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 Aβ and oral health.

Keywords: Microbiome, Alzheimer, amyloid, inflammation, saliva, biomarker.