Written by Charlotte Harrison, Science Writer.
Early detection of Parkinson’s disease (PD) will mean that future therapies have a better chance of working. A new study led by scientists at Purdue University has identified new PD biomarkers in extracellular vesicles (EVs) from urine samples.
If the results stand up to further evaluation and validation studies, the method could offer a non-invasive and simple way of diagnosing Parkinson’s at an early stage.
Biomarker search
The researchers focused on EVs as a source of biomarkers. These lipid bilayer-coated nanoparticles are secreted by all cells, and previous studies indicate that brain-derived EVs can be found in urine.
Emerging evidence indicates that EVs found in biofluids contain a diverse collection of potential biomarkers for neurodegenerative diseases.
The researchers quest to find biomarkers centred on LRRK2 (leucine-rich repeat kinase 2), as mutations in this gene are a known risk factor for PD. They used a proteomics strategy on 138 urine samples from four groups of people: healthy individuals, PD patients with the LRRK2 G2019S mutation, PD patients without the G2019S mutation and healthy people with the G2019S mutation.
Putative biomarkers
Overall, the researchers identified and quantified 4476 unique proteins and 2680 unique phosphoproteins that were elevated in PD. This collection of proteins included those known to be involved in key PD pathways, such as the autophagy pathway, as well as proteins involved in the formation of amyloid fibrils, neuronal cell death and neuroinflammation.
A list of the candidate biomarkers from the four groups of people — that the authors substantiated by machine learning, performance assessment, clinical correlation and/or network analysis — can be found in TABLE 4 of the paper.
Of note, the researchers partially validated several of the candidate biomarkers using parallel reaction monitoring and an immunoassay in samples from a new cohort of patients and controls. In this part of the study, putative biomarkers including the nuclear ribonucleoprotein HNRNPA1, the nuclear transcription factor HNF4A and amyloid precursor protein were upregulated in PD patients.
The promise of EVs
The study adds to other recent findings showing that biofluid-derived EVs are a promising source of disease biomarkers.
“This kind of analysis [based on EVs] opens a new frontier in non-invasive diagnostics development,” said lead author Anton Iliuk in a press release. “It’s showing that biomarkers previously thought to be undetectable have become uncovered and do a really good job of differentiating disease from non-disease state.”
