Study Rationale:

Pathogenic alpha-synuclein (aSyn) aggregates have been recently been detected in spinal fluid of people with Parkinson’s disease where its concentration shows potential to be a biomarker or indicator of Parkinson’s. This application is to dramatically improve on existing alpha-synuclein detection techniques (PMCA and RT-QuIC) by substantially decreasing assay time, increasing detection sensitivity, and determining if the assay will work on more conveniently obtained biosamples that include blood or urine. Our single-molecule counting methods will provide new information on the “fingerprint” of aggregates found in people with Parkinson’s disease.

Hypothesis:

We recently created AttoBright, a device that counts the number and the size of Synuclein aggregates in biological fluids. This method is 200,000 fold more sensitive than current assays, and we will develop standard protocols to be used in hospital for routine detection of PD from blood or urine samples.

Study Design:

We designed a plug-and-play microscope that brings single-molecule counting capabilities to non-specialists. We used 3D printing to produce and duplicate inexpensive instruments with high fidelity, enabling distribution to other laboratories.

Our instrument detects aggregates faster than any methods currently available but also provides quantitative and precise information on the number and size of the protein aggregates. Thanks to this grant, we will establish this new profiling of PD biomarkers as a routine test. We will validate our protocols by using purified reference samples from MJFF, on two different instruments in two different institutes, before accessing samples from MJFF donors with Parkinson’s.

Impact on Diagnosis/Treatment of Parkinson’s disease:

This project seeks to demonstrate that the new single-molecule detection capabilities of the AttoBright will allow rapid, sensitive and reliable detection of pathogenic alpha-synuclein aggregates in either blood (serum or plasma) or urine. The in-depth aggregate profiling produced will provide preliminary evidence of being informative for either diagnosis and/or measuring disease status of people with Parkinson’s. The sensitivity afforded may additionally provide the potential for early diagnosis in the pre-motor phase.

Research Presentation

UNSW research team Yann Gambin and Emma Sierecki shared progress on their research study looking at Single Molecule Detection of Oligomeric Synuclein in biofluids at our first Virtual Research Forum last week. See the slide presentation to learn more about their progress in identifying a reliable biomarker of Parkinson’s disease for earlier detection and quantitative assessment of disease progression.