# Oral Cavity and Brain Cross-talk in Alzheimer's Disease

> **NIH NIH RF1** · UNIVERSITY OF NORTH DAKOTA · 2021 · $1,230,093

## Abstract

Summary
Although Alzheimer’s disease (AD) is an age-associated neurodegenerative disease, continuing evidence
demonstrates pathophysiology outside of the brain. This suggests a more complex process of disease with
systemic manifestations as well. Numerous studies now demonstrate that changes in the oral cavity have a
relationship with AD. Human patients have elevated salivary Aβ concentrations and reported problems with
saliva flow. In addition, periodontal disease, tooth loss, and overall poor oral health are all positive risk factors
for AD. This suggests that AD and periodontal health may have a reciprocal relationship. Using two different
transgenic mouse amyloidosis models of AD, APP/PS1 and AppNL-G-F mice, we verified not only Aβ secretion in
saliva, but a unique disease-associated oral microbiome and enamel thinning and increased cavities compared
to wild type controls. Based upon these findings and prior work by others, we hypothesize that that oral cavity
changes are a peripheral manifestation of AD contributing to disease progression. We will continue using the
AppNL-G-F mouse line to fully define oral health across age and disease stage in the first aim. In the second aim
we will determine whether salivary secretion of Aβ is needed for the oral dysbiosis and decline in oral health in
the AD line. In the third aim we will determine whether the oral dysbiosis is specifically responsible for the
decline in oral health and brain presentation of disease in the mice. This study will define an innovative
mechanism demonstrating that oral cavity dysbiosis and dysfunction is a characteristic of disease which also
contributes to AD progression. We expect to find that salivary Aβ secretion contributes to oral dysbiosis and
changing the oral microbiome is sufficient to ameliorate disease presentation in the brain. This will demonstrate
a new bi-directional understanding of disease involving a mouth-brain axis.

## Key facts

- **NIH application ID:** 10231824
- **Project number:** 1RF1AG072727-01
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** Colin K Combs
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,230,093
- **Award type:** 1
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231824

## Citation

> US National Institutes of Health, RePORTER application 10231824, Oral Cavity and Brain Cross-talk in Alzheimer's Disease (1RF1AG072727-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10231824. Licensed CC0.

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