Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases: An international overview

AmanPreet Badhwar, Université de Montréal, Canada
Yael Hirschberg, University of Antwerp, Belgium
Natalia Valle-Tamayo, Biomedical Research Institute Sant Pau, Spain
Florencia Iulita, Biomedical Research Institute Sant Pau, Spain
Chinedu Momoh, Aga Khan University
Anna Matton, Imperial College London, UK
Rawan Tarawneh, University of New Mexico, USA
Robert Rissman, VA San Diego Healthcare System, USA
Aurélie Ledreux, University of Colorado Anschutz Medical Campus, USA
Charisse Winston, Keck School of Medicine of the University of Southern California, USA

Abstract

INTRODUCTION Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols.

METHODS NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type-specificity, extracellular domains (ECD+), and presence in EV-databases.

RESULTS A total of 82.1% of studies used polymer-based (ExoQuick) EV-enrichment, and 92.3% used L1CAM for IP-based BEV-enrichment. Centrifugation times differed across studies. A total of 26.8% of 82 proteins systematically identified were CNS-specific: 50% ECD+, 77.3% were listed in EV-databases.

CONCLUSIONS We identified protocol steps requiring standardization, and recommend additional CNS-specific proteins that can be used for BEV-enrichment or as BEV-biomarkers.