# Mechanisms of Developmental Plasticity in the Mammalian Olfactory System

> **NIH NIH R01** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2020 · $305,740

## Abstract

Project Summary
 Alzheimer’s Disease (AD) has devastating consequences on an individual’s wellbeing,
community and society. The root cause of AD has not been clearly elucidated. The amyloid protein
Aβ42 has been associated with AD pathology in form amyloid plaques that are thought to cause
neuronal death in Alzheimer’s patients. Intensive research has identified the α-, β and γ-
secretases as processing enzymes that process the amyloid precursor protein (APP) to produce
soluble forms of APP, Aβ proteins and intracellular signaling domains. However, how APP
processing is controlled and modulated by other proteins, and how different forms of the APP
proteolytic product function, remains unclear.
 In this supplemental application, we propose to identify the interaction partners of APP, a
mutant and pathogenic form of APP, and their cleavage products, to elucidate pathways involved
in the trafficking and processing of APP, and the function of various proteolytic products under
normal and pathological conditions. We will utilize APEX2 fusion proteins, a novel approach to
allow extremely accurate labeling of closely associated protein to achieve this goal. We will
conduct this set of experiments in the mouse olfactory system. In Alzheimer’s disease, olfactory
dysfunction is one of the earliest manifestations of pathology. Expression of mutant forms of APP
causes dramatic alteration of axon projection patterns and synaptic connections. The physical
separation of the olfactory sensory neurons and their axons in different compartments make it an
easily accessible system to dissociate protein functions in the axons from those in the cell body.
This study will provide much needed in vivo examination of pathways that process and interact
with APP.
 This study is relevant to the parent grant. The main goal of the parent grant is to understand
the cellular and molecular mechanisms of the development plasticity that permit precise neuronal
connections in the brain. During early postnatal brain development, a high level of plasticity allows
the neurons to make precise and functional connections. This plasticity declines in the adults,
impairing the ability of the nervous system to repair damages and restore function. The specific
goals of the parent study are to identify the cellular and molecular mechanisms underlying axon
targeting in early development and to identify the mechanism that controls the critical period in
the mouse olfactory system. This supplement will extend the study to the function of APP and
Aβ42 to understand pathological conditions that interfere with developmental plasticity.

## Key facts

- **NIH application ID:** 10119618
- **Project number:** 3R01DC016696-03S1
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Congrong Ron Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $305,740
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119618

## Citation

> US National Institutes of Health, RePORTER application 10119618, Mechanisms of Developmental Plasticity in the Mammalian Olfactory System (3R01DC016696-03S1). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10119618. Licensed CC0.

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