RT Journal Article
SR Electronic
T1 Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e866
DO 10.1212/NXI.0000000000000866
VO 7
IS 6
A1 Elena Vacchi
A1 Jacopo Burrello
A1 Dario Di Silvestre
A1 Alessio Burrello
A1 Sara Bolis
A1 Pierluigi Mauri
A1 Giuseppe Vassalli
A1 Carlo W. Cereda
A1 Cinthia Farina
A1 Lucio Barile
A1 Alain Kaelin-Lang
A1 Giorgia Melli
YR 2020
UL http://nn.neurology.org/content/7/6/e866.abstract
AB 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.AP=atypical parkinsonism; AP-Tau=atypical parkinsonism with tauopathies; AUC=area under the curve; BDI-II=Beck Depression Inventory II; CBD=corticobasal degeneration; EV=extracellular vesicle; HC=healthy control; H&Y=Hoehn and Yahr scale; KEGG=Kyoto Encyclopedia of Genes and Genomes; LEDD=levodopa equivalent daily dose; MCSP=melanoma-associated chondroitin sulfate proteoglycan; MDS-UPDRS=Movement Disorder Society–Unified Parkinson's Disease Rating Scale; MFI=median fluorescence intensity; MoCA=Montreal Cognitive Assessment; MSA=multiple system atrophy; nMFI=normalized median fluorescence intensity; NTA=nanoparticle tracking analysis; PD=Parkinson disease; PPI=protein-protein interaction; PSP=progressive supranuclear palsy; RF=random forest; ROC=receiver operating characteristic; TSG101=tumor susceptibility gene 101