# Enhancing diagnosis of Parkinson's disease and multiple system atrophy via detection of alpha-synuclein seeding activity

> **NIH VA IK2** · VA MEDICAL CENTER - LEXINGTON, KY · 2021 · —

## Abstract

Synucleinopathies such as Parkinson's disease (PD) and multiple systems atrophy (MSA) involve abnormal
accumulation of the protein alpha-synuclein (α-syn). Although it has been nearly two centuries since PD was
first described, a dearth of biomarkers has greatly impeded progress toward development of disease-modifying
treatments and accurate and early diagnosis. This proposal is based on the hypothesis that pathology in these
diseases propagates through the brain via a mechanism in which transcellular movement of misfolded α-syn
protein aggregates or “seeds” occurs. There is also evidence that pathogenic α-syn has diverse structures in
diseases such as PD or MSA, that may underlie the clinical and pathologic differences seen in these
synucleinopathies. This proposal utilizes a novel cell-based assay that has been shown to detect and quantify
abnormal α-syn seeding activity that differs both biochemically and structurally in brain extracts from patients
with PD and MSA. In this project we propose to (1) optimize the ability to detect aggregated forms of α-syn
utilizing genetic manipulation of a cell-based sensor, (2) utilize cutting edge molecular and imaging techniques
to parse out differences between α-syn in the synucleinopathies MSA and PD, and (3) determine whether α-syn
seeding activity in blood components of patient samples can serve as a marker for clinical disease progression.
The implications of this work include facilitation of diagnosis and therapeutics for patients with PD and MSA.
The applicant is an Assistant Professor in the Department of Neurology at University of Kentucky, who is firmly
committed to an academic career as an independent translational scientist in the area of neurodegenerative
disease. The proposed training will take advantage of the rich and collaborative environment at the VA, the
excellent clinical documentation and records system, and the very relevant patient population affected by these
diseases and followed in clinic at the VA: all are factors that are integral and crucial to the success of this
proposal. Training will be conducted under the direction of an experienced mentor team. Dr. John Slevin, will be
the primary mentor, and has over 40 years of expertise in clinical research in Movement Disorders and holds a
Merit Award at the VA in basic science research. Dr. Sidney Whiteheart and Dr. Haining Zhu will serve as co-
mentors. They are experts in platelet biochemistry and abnormal protein aggregation, respectively, hold Merit
Awards in their fields, and are also faculty in the Department of Molecular and Cellular Biochemistry at University
of Kentucky. These mentors have been specially selected to advance the candidate’s knowledge of molecular
techniques for investigating aggregated proteins in peripheral fluids of patients with movement disorders.
Training during this proposal includes advanced genetic, molecular, and imaging-based techniques for protein
amplification and detection, and techniques for is...

## Key facts

- **NIH application ID:** 10137075
- **Project number:** 5IK2BX004883-02
- **Recipient organization:** VA MEDICAL CENTER - LEXINGTON, KY
- **Principal Investigator:** Tritia Yamasaki
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137075

## Citation

> US National Institutes of Health, RePORTER application 10137075, Enhancing diagnosis of Parkinson's disease and multiple system atrophy via detection of alpha-synuclein seeding activity (5IK2BX004883-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10137075. Licensed CC0.

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