Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease

Neurol Neuroimmunol Neuroinflamm. 2020 Aug 12;7(6):e866. doi: 10.1212/NXI.0000000000000866. Print 2020 Nov.


Objective: To develop a diagnostic model based on plasma-derived extracellular vesicle (EV) subpopulations in Parkinson disease (PD) and atypical parkinsonism (AP), we applied an innovative flow cytometric multiplex bead-based platform.

Methods: Plasma-derived EVs were isolated from PD, matched healthy controls, multiple system atrophy (MSA), and AP with tauopathies (AP-Tau). The expression levels of 37 EV surface markers were measured by flow cytometry and correlated with clinical scales. A diagnostic model based on EV surface markers expression was built via supervised machine learning algorithms and validated in an external cohort.

Results: Distinctive pools of EV surface markers related to inflammatory and immune cells stratified patients according to the clinical diagnosis. PD and MSA displayed a greater pool of overexpressed immune markers, suggesting a different immune dysregulation in PD and MSA vs AP-Tau. The receiver operating characteristic curve analysis of a compound EV marker showed optimal diagnostic performance for PD (area under the curve [AUC] 0.908; sensitivity 96.3%, specificity 78.9%) and MSA (AUC 0.974; sensitivity 100%, specificity 94.7%) and good accuracy for AP-Tau (AUC 0.718; sensitivity 77.8%, specificity 89.5%). A diagnostic model based on EV marker expression correctly classified 88.9% of patients with reliable diagnostic performance after internal and external validations.

Conclusions: Immune profiling of plasmatic EVs represents a crucial step toward the identification of biomarkers of disease for PD and AP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Surface
  • Biomarkers / blood
  • Case-Control Studies
  • Cross-Sectional Studies
  • Extracellular Vesicles / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Multiple System Atrophy / blood
  • Multiple System Atrophy / classification
  • Multiple System Atrophy / diagnosis
  • Multiple System Atrophy / immunology
  • Parkinson Disease / blood
  • Parkinson Disease / classification
  • Parkinson Disease / diagnosis
  • Parkinson Disease / immunology
  • Parkinsonian Disorders / blood
  • Parkinsonian Disorders / classification
  • Parkinsonian Disorders / diagnosis*
  • Parkinsonian Disorders / immunology*
  • Protein Interaction Maps
  • Sensitivity and Specificity
  • Supervised Machine Learning
  • Tauopathies / blood
  • Tauopathies / classification
  • Tauopathies / diagnosis*
  • Tauopathies / immunology*


  • Antigens, Surface
  • Biomarkers