# Development of Blood Based Diagnosis of Parkinson's Disease

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $427,750

## Abstract

PROJECT SUMMARY/ABSTRACT
Parkinson's disease (PD) is a devastating neurodegenerative disorder which has no cure or disease-modifying
therapy. One of the greatest obstacles for developing a disease-modifying therapy for PD is the lack of early
diagnosis. To date, there is no definite, sensitive and predictive laboratory test available that can identify
individuals well before they show clinical manifestations. The availability of early diagnosis of PD would be of
utmost importance for the development of a disease-modifying or preventive therapies before the irreversible
brain damage has already occurred. The pathological hallmark of PD is the cytoplasmic deposition of amyloid-
like aggregates mainly composed of alpha-synuclein (αSyn) termed as Lewy bodies. Compelling evidence
suggests that the central event in PD is misfolding and aggregation of αSyn. The misfolding and aggregation of
αSyn follows a nucleation-dependent mechanism which involves the formation of several intermediate species
including soluble αSyn oligomers and protofibrils. Alpha-synuclein oligomerization is a key event in PD
pathogenesis that begins years or decades before the appearance of clinical signs. Most importantly, recent
studies have suggested that these αSyn oligomers circulate in biological fluids such as cerebrospinal fluid
(CSF) and blood. Thus, we hypothesize that the detection of these circulating misfolded αSyn oligomers holds
promise for diagnosis of PD and related synucleinopathies.
We have recently reported protein misfolding cyclic amplification (PMCA) assay for the detection of misfolded
αSyn oligomers in CSF. Using this PMCA technology, we have been able to differentiate PD patients from
control individuals affected by other neurodegenerative (ND) or non-neurodegenerative (NND) disorders with
high specificity and sensitivity. The main goal of this application is to expand the applicability of this
technology to detect small amounts of αSyn oligomers present in blood so that a cheap, noninvasive and
reliable diagnostic test could be developed. To achieve this goal, we will optimize the assay conditions for
sensitive and specific detection of αSyn oligomers in human blood plasma. Then, we will use well-
characterized plasma samples from PD patients, individuals affected with other synucleinopathies, and healthy
controls. Next, the sensitivity and specificity of αSyn-PMCA for PD will be evaluated using a large number of
plasma samples from PD patients, age-matched healthy controls, and individuals affected from ND and NND.
Finally, we will attempt to correlate the kinetic parameters of αSyn-PMCA with clinical data at different stages
of PD.
The findings obtained here will lay the foundation for the development of low cost, non-invasive diagnosis of
individuals at risk of developing PD and other synucleinopathies. Our findings will not only help to understand
the mechanisms implicated in PD progression but also will provide a window for disease prevention and
in...

## Key facts

- **NIH application ID:** 9876517
- **Project number:** 1R21NS114884-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Mohammad Shahnawaz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,750
- **Award type:** 1
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876517

## Citation

> US National Institutes of Health, RePORTER application 9876517, Development of Blood Based Diagnosis of Parkinson's Disease (1R21NS114884-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9876517. Licensed CC0.

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