Profiling Inflammatory Extracellular Vesicles in Plasma and Cerebrospinal Fluid: An Optimized Diagnostic Model for Parkinson’s Disease

Abstract

Extracellular vesicles (EVs) play a central role in intercellular communication, which is relevant for inflammatory and immune processes implicated in neurodegenerative disorders, such as Parkinson’s Disease (PD). We characterized and compared distinctive cerebrospinal fluid (CSF)-derived EVs in PD and atypical parkinsonisms (AP), aiming to integrate a diagnostic model based on immune profiling of plasma-derived EVs via artificial intelligence. Plasma- and CSF-derived EVs were isolated from patients with PD, multiple system atrophy (MSA), AP with tauopathies (AP-Tau), and healthy controls. Expression levels of 37 EV surface markers were measured by a flow cytometric bead-based platform and a diagnostic model based on expression of EV surface markers was built by supervised learning algorithms. The PD group showed higher amount of CSF-derived EVs than other groups. Among the 17 EV surface markers differentially expressed in plasma, eight were expressed also in CSF of a subgroup of PD, 10 in MSA, and 6 in AP-Tau. A two-level random forest model was built using EV markers co-expressed in plasma and CSF. The model discriminated PD from non-PD patients with high sensitivity (96.6%) and accuracy (92.6%). EV surface marker characterization bolsters the relevance of inflammation in PD and it underscores the role of EVs as pathways/biomarkers for protein aggregation-related neurodegenerative diseases.

Risk stratification of patients with SARS-CoV-2 by tissue factor expression in circulating extracellular vesicles

“…[ 5 ] We took advantage from reproducible flow cytometer assay that has been previously standardized and validated for the detection and characterization of EV surface signatures. [ [16] , [17] , [18] , [19] ]…”

Surface protein profiling of milk and serum extracellular vesicles unveil body fluid and cell-type signatures and insights on vesicle biogenesis

“…Since 2018, this assay has been used for surface protein profiling of EVs from various body fluids, i.e. blood plasma 19,[37][38][39][40][41] , serum 19,[42][43][44] , urine 44 , cerebral spinal fluid 38 and lymphatic drain fluid 45 of healthy subjects and patients, using a wide variety of EV enrichment/purification protocols, EV quantification methods and input EV amounts. To our knowledge no studies have been reported on the use of this assay on EVs purified from different body fluids collected on the same day from the same donor, isolated by similar protocols and analysed by pan-tetraspanin as well as single tetrapsanin detection.…”

Analysis of Circulating Immune Subsets in Primary Colorectal Cancer

“…The primary limitation of this study is that the number of patients is low, which could compromise the validity of our diagnostic model. However, recently, several robust studies constructed the diagnostic model, based on a comparable size of subjects [ 49 , 50 , 51 ]. In terms of the advanced age in CRC patients, compared to healthy controls, it is difficult to completely eradicate the potential age-related bias in immune cells.…”