# Olfactory Epithelium Responses to Human APOE Alleles

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2024 · $191,250

## Abstract

Project Summary:
Deficits in olfaction were recognized decades ago as early symptoms in people with incipient Alzheimer’s
Disease. However, these discoveries have had less impact than hoped on the study, diagnosis, and treatment
of this disease. Though central nervous system olfactory pathways suffer the plaques and/or tangles that are
characteristic of late-stage disease, these symptoms do not set the olfactory system apart from other foci of
research into Alzheimer’s Disease. Perhaps because the regenerative capacity of the olfactory epithelium
obscured the vulnerability of olfactory sensory neurons to Alzheimer’s Disease, especially the early events
leading to the neurodegeneration characteristic of the disease, study of how the olfactory epithelium is
impacted by Alzheimer’s Disease languished. Clear evidence that the olfactory sensory neurons in the
epithelium are susceptible to factors that cause or increase risk of Alzheimer’s Disease has recently emerged,
however. These findings demonstrate that the olfactory epithelium is a worthy model of how risk factors for
Alzheimer’s Disease affect neurons and their supporting cells. Thus far the data correlate well with effects in
the brain, evidence that the olfactory epithelium may be a bellwether for events transpiring in the central
nervous system. The accessibility of the olfactory epithelium for biopsy to assess disease progression in
individuals and to drugs that cannot pass the blood brain barrier further elevates the significance of the
olfactory epithelium as a model. This project investigates the effects of a critical risk factor for Alzheimer’s
Disease, APOE genotype, on the olfactory epithelium and its olfactory sensory neurons. The experiments
focus on identifying early events and the strength of their effects on phenotype and function. It uses mouse
models of the disease, including established genetic models previously used to investigate effects in the brain
and a novel model that allows switching at will from a neurodegenerative genotype to a neuroprotective
genotype. The latter allows testing of whether cellular and molecular events associated with vulnerability to
Alzheimer’s Disease can be prevented or reversed by in vivo genetic manipulation, outcomes that would inform
and inspire further work towards curing this disease.

## Key facts

- **NIH application ID:** 10817135
- **Project number:** 5R21AG082081-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Timothy S McClintock
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,250
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817135

## Citation

> US National Institutes of Health, RePORTER application 10817135, Olfactory Epithelium Responses to Human APOE Alleles (5R21AG082081-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10817135. Licensed CC0.

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