# Characterizing age-related decline of neural circuits by single-cell profiling

> **NIH NIH R00** · BAYLOR COLLEGE OF MEDICINE · 2022 · $249,000

## Abstract

Summary - Administrative Supplements
(Parent R00 grant - R00AG062746; funding ends on 1/31/2024)
For the Parent R00 grant, I proposed to employ integrated multi-omics methods to characterize
age-related olfactory decline in Drosophila (see more details in the Research Strategy).
Olfactory sensitivity decline is an early symptom of dementia and has a relatively high prevalence in
different types of dementia, almost 100% in Alzheimer’s disease (AD), 90% in Parkinson’s disease and
15% in vascular dementias (1,2). Olfactory dysfunction in Alzheimer’s disease patients has been
documented about 40 years ago (3). Several clinical studies have reported that combining olfactory
function tests with conventional diagnostic methods can significantly increase the prediction accuracy of
Alzheimer’s disease progress (4). Olfactory function test is relatively simple and normally non-invasive,
and thus may be employed as a clinical marker for Alzheimer’s disease. However, olfactory dysfunction
is frequently overlooked by both physicians and patients. One major reason is that it is difficult to
distinguish age-related and Alzheimer’s disease-caused olfactory decline. To overcome this limitation, it
is important to understand how aging and AD impact the olfactory system at the cellular and molecular
level. Unfortunately, so far there is no study systemically addressing this question.
 Drosophila olfactory sensitivity significantly declines during aging and Alzheimer’s disease
models, as in humans, but the mechanism is still a mystery. Here, I propose an extension of current
studies in aging flies to AD fly models (Fig. 1), taking advantage of our accumulated tools and
knowledge in the Drosophila olfactory system, as well as the scRNA-seq and cell-surface
proteomics technologies we recently developed. We aim to characterize how aging and AD
differentially impact olfactory receptor neuron integrity and glia-neuron interaction. Importantly, we will
potentially identify olfactory changes that are specific to AD but not in normal aging condition, so that
we can design specific olfactory function test to distinguish AD from normal aging. Thus, this
supplement on one hand is a natural extension of our studies of the olfactory circuit decline
during normal aging, and on the other hand can shed light into molecular mechanisms of glia-
neuron interactions, dysfunctions of which have been implicated in AD.
1

## Key facts

- **NIH application ID:** 10499126
- **Project number:** 3R00AG062746-04S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Hongjie Li
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,000
- **Award type:** 3
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499126

## Citation

> US National Institutes of Health, RePORTER application 10499126, Characterizing age-related decline of neural circuits by single-cell profiling (3R00AG062746-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10499126. Licensed CC0.

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