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

Autor: Badhwar A; Département de pharmacologie et physiologie, Institut de Génie Biomédical, Faculté de Médecine, Université de Montréal, Montréal, Quebec, Canada.; Multiomics Investigation of Neurodegenerative Diseases (MIND) lab, Centre de recherche de l'Institut Universitaire de Gériatrie, Montréal, Quebec, Canada., Hirschberg Y; Centre for Proteomics, University of Antwerp, Antwerp, Belgium.; Health Unit, Flemish Institute for Technological Research (VITO), Mol, Belgium., Valle-Tamayo N; Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Calle San Quintí, Barcelona, Spain., Iulita MF; Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Calle San Quintí, Barcelona, Spain., Udeh-Momoh CT; Ageing Epidemiology research unit, School of Public Health, Imperial College London, London, UK.; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Solna, Sweden.; Global Brain Health Institute, University of San Francisco Joan and Sanford I. Weill Neurosciences building, San Francisco, California, USA.; Imarisha Centre for Brain Health and Aging, Brain and Mind Institute, Aga Khan University, Nairobi, Kenya., Matton A; Ageing Epidemiology research unit, School of Public Health, Imperial College London, London, UK.; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Solna, Sweden.; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Karolinska Institutet, Solna, Nobels väg, Sweden., Tarawneh RM; Department of Neurology, Center for Memory and Aging, University of New Mexico, Albuquerque, New Mexico, USA., Rissman RA; VA San Diego Healthcare System, San Diego, California, USA.; Department of Physiology and Neuroscience, Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Ledreux A; Department of Neurosurgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Winston CN; Department of Physiology and Neuroscience, Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, San Diego, California, USA., Haqqani AS; National Research Council Canada, Ottawa, Ontario, Canada.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Jul; Vol. 20 (7), pp. 4411-4422. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1002/alz.13823
Abstrakt: 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.
(© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE