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

Abstract

BACKGROUND\nBeta 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.\n\n\nOBJECTIVE\nBased 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.\n\n\nMETHODS\nTo 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.\n\n\nRESULTS\nBoth 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.\n\n\nCONCLUSION\nThese data support the idea that oral microbiome changes exist during AD in addition to changes in salivary Aβ and oral health.