# Differentiation and characterization of conformational alpha-synuclein strains associated with Parkinson's disease and related synucleinopathies

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $517,505

## Abstract

Synucleinopathies are a diverse group of neurodegenerative diseases characterized by misfolding,
aggregation and accumulation of misfolded alpha-synuclein (αSyn) which include Parkinson‘s
disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB). Despite
sharing the same pathological protein, different clinical and pathological phenotypes are typically
observed in different synucleinopathies. One of the main obstacles to develop effective treatments
for synucleinopathies is the lack of an early diagnosis before the onset of brain damage and clinical
symptoms of the disease. Clinically, it is very challenging to discriminate between some of the
synucleinopathies (e.g. PD and MSA), especially at early stages of the disease. This is an
important problem because these diseases have different prognosis and modes of treatment.
Recently, we developed the protein misfolding cyclic amplification (PMCA, also known as RT-
QuIC) technology for highly sensitive and specific detection of αSyn oligomers in biological fluids of
patients affected by synucleinopathies. αSyn-PMCA utilizes the prion-like seeding mechanism to
cyclically amplify the process of protein misfolding, enabling the efficient amplification of small
quantities of αSyn oligomers, facilitating their detection. We have evidence that the product of
αSyn-PMCA coming from CSF samples of patients affected by PD and MSA can be experimentally
distinguished. Thus, we hypothesize that αSyn aggregates associated with different
synucleinopathies correspond to different conformational strains/ sub-strains of αSyn that can be
faithfully amplified by αSyn-PMCA and the product can be differentiated by their biochemical,
structural and biological properties. In this study, our main goal is to detect, differentiate and
amplify minute amounts of αSyn strains/ sub-strains from biological fluids and brain tissue of
patients with synucleinopathies by an in-vitro seeding/ amplification assay, and characterize these
αSyn conformational aggregates using various biochemical, structural, and biological techniques.
The findings obtained here will lay the foundation towards the development of a biochemical test
for differential diagnosis of synucleinopathies by sensitive and specific detection of different αSyn
strains/sub-strains, which will help in patients’ stratification, target enrollment for clinical trial and
personalized treatment.

## Key facts

- **NIH application ID:** 10460906
- **Project number:** 5R01NS119689-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Sandra Pritzkow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $517,505
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460906

## Citation

> US National Institutes of Health, RePORTER application 10460906, Differentiation and characterization of conformational alpha-synuclein strains associated with Parkinson's disease and related synucleinopathies (5R01NS119689-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460906. Licensed CC0.

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