Proteomic analysis of urinary extracellular vesicles reveal biomarkers for neurologic disease.
Abstract
BACKGROUND:Extracellular vesicles (EVs) harbor thousands of proteins that hold promise
for biomarker development. Usually difficult to purify, EVs in urine are relatively
easily obtained and have demonstrated efficacy for kidney disease prediction. Herein,
we further characterize the proteome of urinary EVs to explore the potential for biomarkers
unrelated to kidney dysfunction, focusing on Parkinson's disease (PD). METHODS:Using
a quantitative mass spectrometry approach, we measured urinary EV proteins from a
discovery cohort of 50 subjects. EVs in urine were classified into subgroups and EV
proteins were ranked by abundance and variability over time. Enriched pathways and
ontologies in stable EV proteins were identified and proteins that predict PD were
further measured in a cohort of 108 subjects. FINDINGS:Hundreds of commonly expressed
urinary EV proteins with stable expression over time were distinguished from proteins
with high variability. Bioinformatic analyses reveal a striking enrichment of endolysosomal
proteins linked to Parkinson's, Alzheimer's, and Huntington's disease. Tissue and
biofluid enrichment analyses show broad representation of EVs from across the body
without bias towards kidney or urine proteins. Among the proteins linked to neurological
diseases, SNAP23 and calbindin were the most elevated in PD cases with 86% prediction
success for disease diagnosis in the discovery cohort and 76% prediction success in
the replication cohort. INTERPRETATION:Urinary EVs are an underutilized but highly
accessible resource for biomarker discovery with particular promise for neurological
diseases like PD.
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https://hdl.handle.net/10161/19466Published Version (Please cite this version)
10.1016/j.ebiom.2019.06.021Publication Info
Wang, Shijie; Kojima, Kyoko; Mobley, James A; & West, Andrew B (2019). Proteomic analysis of urinary extracellular vesicles reveal biomarkers for neurologic
disease. EBioMedicine, 45. pp. 351-361. 10.1016/j.ebiom.2019.06.021. Retrieved from https://hdl.handle.net/10161/19466.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Andrew Bradley West
Professor of Pharmacology and Cancer Biology
I am a tenured Professor with a primary appointment in Pharmacology and Cancer Biology,
secondary appointments in Neurology and Neurobiology, and I serve as the director
of the Duke Center for Neurodegeneration and Neurotherapeutics. Our main research
efforts in the laboratory have focused on LRRK2 and alpha-synuclein in critical mechanisms
and biomarkers in neurodegeneration and as possible therapeutic targets for disease
modification strategies. I am a founding member of the NINDS Parkinson

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