Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases : An international overview
Badhwar, AmanPreet (Centre de recherche de l'Institut Universitaire de Gériatrie)
Hirschberg, Yael (University of Antwerp)
Valle-Tamayo, Natalia (Institut de Recerca Sant Pau)
Iulita, M. Florencia (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Udeh-Momoh, Chinedu (Aga Khan University)
Matton, Anna (Karolinska Institutet (Estocolm, Suècia))
Tarawneh, Rawan (University of New Mexico)
Rissman, Robert A. (Keck School of Medicine of the University of Southern California)
Ledreux, Aurélie (University of Colorado Anschutz Medical Campus)
Winston, Charisse (University of Southern California)
Haqqani, Arsalan (National Research Council Canada)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	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. Highlights: Across NDDs, we identified protocols commonly used for EV/BEV enrichment from blood. We identified protocol steps showing variability that require harmonization. We assessed CNS-specificity of proteins used for BEV-enrichment or found in BEV cargo. CNS-specific EV proteins with ECD+ or without were identified. We recommend evaluation of blood-BEV enrichment using these additional ECD+ proteins.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Age-related neurodegenerative diseases ; Biofluid based biomarkers ; Blood ; Brain-derived extracellular vesicles ; Exosomes ; Immunoprecipitation-based enrichment ; Microvesicles ; Novel biomarkers ; Protocol variability
Publicat a:	Alzheimer's & dementia, Vol. 20 Núm. 7 (july 2024) , p. 4411-4422, ISSN 1552-5279

DOI: 10.1002/alz.13823
PMID: 38864416

12 p, 2.0 MB

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