title: Identification of distinct circulating exosomes in Parkinson's disease.
abstract: OBJECTIVE
  Whether circulating microvesicles convey bioactive signals in neurodegenerative diseases remains currently unknown. In this study, we investigated the biochemical composition and biological function of exosomes isolated from sera of patients with Parkinson's disease (PD).
  
  
  METHODS
  Proteomic analysis was performed on microvesicle preparations from grouped samples of patients with genetic and sporadic forms of PD, amyotrophic lateral sclerosis, and healthy subjects. Nanoparticle-tracking analysis was used to assess the number and size of exosomes between patient groups. To interrogate their biological effect, microvesicles were added to primary rat cortical neurons subjected to either nutrient deprivation or sodium arsenite.
  
  
  RESULTS
  Among 1033 proteins identified, 23 exosome-associated proteins were differentially abundant in PD, including the regulator of exosome biogenesis syntenin 1. These protein changes were detected despite similar exosome numbers across groups suggesting that they may reflect exosome subpopulations with distinct functions. Accordingly, we showed in models of neuronal stress that Parkinson's-derived microvesicles have a protective effect.
  
  
  CONCLUSIONS
  Collectively, these data suggest for the first time that immunophenotyping of circulating exosome subpopulations in PD may lead to a better understanding of the systemic response to neurodegeneration and the development of novel therapeutics.
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Tomlinson
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Nuffield Department of Medicine, Target Discovery Institute, University of Oxford Oxford, United Kingdom.
authors.forename: Roman
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom.
authors.forename: Ronny
authors.initials: R
authors.lastname: Heidasch
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford Oxford, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Gardiner
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom.
authors.forename: Samuel
authors.initials: S
authors.lastname: Evetts
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom ; Oxford Parkinson's Disease Centre, University of Oxford Oxford, United Kingdom.
authors.forename: Michele
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, United Kingdom ; Oxford Parkinson's Disease Centre, University of Oxford Oxford, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Wade-Martins
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Turner
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Morris
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom ; Oxford Parkinson's Disease Centre, University of Oxford Oxford, United Kingdom.
authors.forename: Kevin
authors.initials: K
authors.lastname: Talbot
authors.affiliation: Nuffield Department of Medicine, Target Discovery Institute, University of Oxford Oxford, United Kingdom ; Oxford Parkinson's Disease Centre, University of Oxford Oxford, United Kingdom.
authors.forename: Benedikt M
authors.initials: BM
authors.lastname: Kessler
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford Oxford, United Kingdom ; Oxford Parkinson's Disease Centre, University of Oxford Oxford, United Kingdom.
authors.forename: George K
authors.initials: GK
authors.lastname: Tofaris