# Relationship between inner ear function, amyloid precursor protein and CNS pathology

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $433,125

## Abstract

Clinical studies have suggested a link between the loss of sensory function in the inner ear and the
development of Alzheimer’s disease. The biological basis of this association is not clear. Neurodegeneration
that occurs in Alzheimer’s disease (AD) appears to be caused by aberrant processing and clustering of protein
fragments derived from amyloid precursor protein (APP) and the microtubule-associated protein Tau.
Consistent with this notion, certain identified mutations in APP and Tau are known to greatly increase the risk
of developing AD. The projects outlined here are partly motivated by our observation that high levels of APP
and Tau are also present in the hair cells and afferent neurons of the cochlea and vestibular organs, raising the
possibility that these proteins might contribute to degeneration in the aging inner ear. However, it is equally
possible that inner ear dysfunction is linked to AD because the loss of sensory input from the aging inner ear
increases the likelihood of CNS degeneration and dementia. Experiments proposed here will use established
mouse models of Alzheimer’s disease and engineered deafness to address these issues. In Aim 1, we will
determine whether b-amyloid and Tau deposition and subsequent degeneration occurs in the inner ear.
Experiments in Aim 2 will test whether disruption of inner ear function leads to increased CNS neuropathology
in a mouse model of Alzheimer’s disease. To our knowledge, these will be the first studies to directly examine
the potential relationship between inner ear function and amyloid-related CNS pathology. The outcomes may
reveal a role for APP in degeneration of the inner ear, or indicate that input from the ear affects amyloid
deposition in the CNS. A more complete understanding of the link between inner ear function and Alzheimer’s
disease may also lead to novel diagnostics for the detection of early stage AD in humans.

## Key facts

- **NIH application ID:** 10127112
- **Project number:** 1R21AG067551-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Mark Warchol
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $433,125
- **Award type:** 1
- **Project period:** 2020-09-11 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127112

## Citation

> US National Institutes of Health, RePORTER application 10127112, Relationship between inner ear function, amyloid precursor protein and CNS pathology (1R21AG067551-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10127112. Licensed CC0.

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