# Preclinical Markers of Parkinsonism

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2021 · $625,104

## Abstract

SUMMARY
We have known for some time that α-synuclein aggregates to form insoluble fibrils in pathological conditions
characterized by Lewy bodies, such as Parkinson’s disease (PD), multiple system atrophy, and dementia with
Lewy bodies. People with synucleinopathies desperately need disease modifying therapies, that either slow or
stop neurodegeneration. In order to facilitate the development of new therapies, the fields of neurology, motor
control, neuroimaging, and α-synuclein biomarkers need to join forces to identify disease far earlier, well before
a neurologist currently makes a diagnosis. In Alzheimer’s disease, investigators have defined Mild Cognitive
Impairment (MCI) before dementia and this has unleashed a series of preclinical behavioral, imaging, and
pathologically-relevant markers that have revolutionized how clinical trials are conducted for dementia. This
same type of revolution in early identification is sorely missing, but clearly needed, in the area of Parkinsonism.
In this proposal, we will define a Mild Parkinson Impairment (MPI) using innovative markers that cut across
imaging and physiology. We will study a preclinical model of Parkinsonism, known as rapid eye movement
(REM) behavior disorder (RBD). The reason RBD is a preclinical model of Parkinsonism, is that 50-60% of
patients with RBD go on to develop PD, and the remainder develop either dementia with Lewy bodies or multiple
system atrophy. Individuals with RBD will eventually exhibit clinical Parkinsonism with varying degrees of
severity. Here, we test the central hypothesis that we can identify early cross-sectional and longitudinal markers
of Mild Parkinson Impairment in patients with RBD. Our goal in this proposal is to study patients with RBD prior
to other diagnoses to identify early cross-sectional and longitudinal markers of preclinical Parkinsonism. Based
on our strong preliminary data and our prior work we will: 1) evaluate innovative measures of brainstem functional
magnetic resonance imaging and task-based striatal-cortical functional connectivity; 2) test our robust marker
free-water in the substantia nigra in RBD for the first time; 3) measure a newly developed α-synuclein skin
biomarker called real-time quaking-induced conversion (RT-QuIC) assay; 4) evaluate motor control assays to
define a preclinical mild motor impairment; and 5) follow patients longitudinally after 24 months to determine if
these imaging and physiology markers progress over time in people with RBD.

## Key facts

- **NIH application ID:** 10120080
- **Project number:** 2R01NS058487-11
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Michael S. Jaffee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $625,104
- **Award type:** 2
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120080

## Citation

> US National Institutes of Health, RePORTER application 10120080, Preclinical Markers of Parkinsonism (2R01NS058487-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10120080. Licensed CC0.

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