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Neurobiol Dis. 2018 Nov 5. pii: S0969-9961(18)30534-5. doi: 10.1016/j.nbd.2018.11.002. [Epub ahead of print]

Portrait of blood-derived extracellular vesicles in patients with Parkinson's disease.

Author information

1
Centre de recherche du CHU de Québec, Québec, QC, Canada.
2
Département de mathématiques et génie industriel, École Polytechnique de Montréal, Montréal, QC, Canada.
3
Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, QC, Canada.
4
Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.
5
Centre de recherche du CHU de Québec, Québec, QC, Canada; Département de médecine moléculaire, Université Laval, Québec, QC, Canada.
6
Centre de recherche du CHU de Québec, Québec, QC, Canada; Département de médecine, Université Laval, Département de neurosciences, Hôpital de l'Enfant-Jésus, Québec, QC, Canada.
7
Centre Hospitalier de l'Université de Montréal and Centre de recherche du Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Département de médicine, Université de Montréal, Montréal, QC, Canada.
8
Centre de recherche du CHU de Québec, Québec, QC, Canada; Département de microbiologie-infectiologie et d'immunologie, Université Laval, Québec, QC, Canada. Electronic address: Eric.Boilard@crchudequebec.ulaval.ca.
9
Centre de recherche du CHU de Québec, Québec, QC, Canada; Département de psychiatrie & neurosciences, Université Laval, Québec, QC, Canada. Electronic address: Francesca.Cicchetti@crchul.ulaval.ca.

Abstract

The production of extracellular vesicles (EV) is a ubiquitous feature of eukaryotic cells but pathological events can affect their formation and constituents. We sought to characterize the nature, profile and protein signature of EV in the plasma of Parkinson's disease (PD) patients and how they correlate to clinical measures of the disease. EVs were initially collected from cohorts of PD (n = 60; Controls, n = 37) and Huntington's disease (HD) patients (Pre-manifest, n = 11; manifest, n = 52; Controls, n = 55) - for comparative purposes in individuals with another chronic neurodegenerative condition - and exhaustively analyzed using flow cytometry, electron microscopy and proteomics. We then collected 42 samples from an additional independent cohort of PD patients to confirm our initial results. Through a series of iterative steps, we optimized an approach for defining the EV signature in PD. We found that the number of EV derived specifically from erythrocytes segregated with UPDRS scores corresponding to different disease stages. Proteomic analysis further revealed that there is a specific signature of proteins that could reliably differentiate control subjects from mild and moderate PD patients. Taken together, we have developed/identified an EV blood-based assay that has the potential to be used as a biomarker for PD.

KEYWORDS:

Alpha-synuclein; Blood cells; Erythrocytes; Extracellular vesicles

PMID:
30408591
DOI:
10.1016/j.nbd.2018.11.002

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