# Asymmetric neurodegeneration of central olfactory system in early-stage Parkinsons disease

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2021 · $488,345

## Abstract

Abstract:
At present, pathology studies of Parkinson's disease (PD) have shown that the clinical early stage at diagnosis
is, in fact, at a pathologically late stage with up to 50-70% of dopaminergic neurons depleted in the substantia
nigra. Therefore, there is a critical need for a biomarker capable of detecting pathological changes much
earlier. However, when beginning to address this issue, one must first be able to identify a cohort of at-risk
preclinical subjects who will eventually develop PD, which is not possible without an early marker. Such a
“chicken-and-egg” problem holds back PD research significantly. This application is conceived based on three
well-documented findings: 1) Olfactory dysfunction is prevalent in PD, and central olfactory system is highly
affected by PD pathology, approximately 4 years earlier than the substantia nigra; 2) The clinical symptoms are
always asymmetric at the diagnosis of H&Y stage-I early onset PD, and as the disease progresses to stage II
within a few years, the asymptomatic side of the body inevitably develops motor symptoms; and 3)
Postmortem pathological and our recent in vivo MRI studies have demonstrated the asymmetry of pathological
status in the two hemispheres at the early stage of disease. Combining these findings and facts creates a
unique opportunity to overcome the challenge of identifying preclinical PD subjects, because the asymptomatic
hemisphere in stage-I PD offers a sample at a transitional stage between “preclinical” stage and clinical stage,
and early pathology in the central olfactory system offers a site for potential biomarkers for PD. We
hypothesize that the clinically asymptomatic hemisphere of stage-I PD is at a transitional stage between
“preclinical” and clinical stage, and there is hemispheric asymmetry in functional deficits in the
primary olfactory cortex (POC) of patients at this stage. Using a novel fMRI technique in our preliminary
study of stage-I early onset PD, we have found significant asymmetry in odor-related activation deficit at POC.
In this application, we propose a prospective cohort study of cognitively-normal stage-I early onset PD patients
with olfactory fMRI, morphological MRI of the olfactory bulb (OB) and POC, psychophysical evaluation of smell
functions, and clinical assessment of motor deficits. Our goal is to understand the underlying mechanisms of
olfactory deficit in PD, and its relationship to disease progression. This goal will be accomplished with the
following three specific aims: Specific Aim 1 will test the hypothesis that there is a hemispheric asymmetry in
functional deficit in the POC in H&Y stage-I PD; Specific Aim 2 will test the hypothesis that there is a
hemispheric asymmetry in morphological change of the OB and POC in H&Y stage-I PD; Specific Aim 3 will
test the hypothesis that the functional deficit in the POC and the atrophy of the OB and POC worsen as the
disease progresses in the early stages of PD. A successful outcome of this r...

## Key facts

- **NIH application ID:** 10146491
- **Project number:** 5R01NS099630-05
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Jianli Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $488,345
- **Award type:** 5
- **Project period:** 2017-06-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146491

## Citation

> US National Institutes of Health, RePORTER application 10146491, Asymmetric neurodegeneration of central olfactory system in early-stage Parkinsons disease (5R01NS099630-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146491. Licensed CC0.

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