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

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, AppNL-G-F , and APP/PS1 mice. RESULTS Both male and female AD, AppNL-G-F , and APP/PS1 glands demonstrated robust APP and Aβ immunoreactivity. Female AppNL-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 AppNL-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 AppNL-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.