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Cited by 79Extracellular vesicles in diseaseNanoparticle-Based Drug DeliveryNeuroinflammation and Neurodegeneration Mechanisms

Emergence of Extracellular Vesicles as “Liquid Biopsy” for Neurological Disorders: Boom or Bust

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Kumar, Ashish, Nader, Michael A., Deep, Gagan·2024·Pharmacological Reviews
DOI 10.1124/pharmrev.122.000788PMC PMC10877757
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Abstract

Extracellular vesicles (EVs) have emerged as an attractive liquid biopsy approach in the diagnosis and prognosis of multiple diseases and disorders. The feasibility of enriching specific subpopulations of EVs from biofluids based on their unique surface markers has opened novel opportunities to gain molecular insight from various tissues and organs, including the brain. Over the past decade, EVs in bodily fluids have been extensively studied for biomarkers associated with various neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, major depressive disorders, substance use disorders, human immunodeficiency virus-associated neurocognitive disorder, and cancer/treatment-induced neurodegeneration. These studies have focused on the isolation and cargo characterization of either total EVs or brain cells, such as neuron-, astrocyte-, microglia-, oligodendrocyte-, pericyte-, and endothelial-derived EVs from biofluids to achieve early diagnosis and molecular characterization and to predict the treatment and intervention outcomes. The findings of these studies have demonstrated that EVs could serve as a repetitive and less invasive source of valuable molecular information for these neurological disorders, supplementing existing costly neuroimaging techniques and relatively invasive measures, like lumbar puncture. However, the initial excitement surrounding blood-based biomarkers for brain-related diseases has been tempered by challenges, such as lack of central nervous system specificity in EV markers, lengthy protocols, and the absence of standardized procedures for biological sample collection, EV isolation, and characterization. Nevertheless, with rapid advancements in the EV field, supported by improved isolation methods and sensitive assays for cargo characterization, brain cell-derived EVs continue to offer unparallel opportunities with significant translational implications for various neurological disorders. SIGNIFICANCE STATEMENT: Extracellular vesicles present a less invasive liquid biopsy approach in the diagnosis and prognosis of various neurological disorders. Characterizing these vesicles in biofluids holds the potential to yield valuable molecular information, thereby significantly impacting the development of novel biomarkers for various neurological disorders. This paper has reviewed the methodology employed to isolate extracellular vesicles derived from various brain cells in biofluids, their utility in enhancing the molecular understanding of neurodegeneration, and the potential challenges in this research field.

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Authors
Kumar, A., Nader, M. A., & Deep, G.
Affiliations
Atrium Health Wake Forest Baptist (US)
Corresponding author
Deep, Gagan
ORCID
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2024-03
Volume
76
Issue
2
Pages
199-227
ISSN
0031-6997 (ISSN-L)
DOI
10.1124/pharmrev.122.000788
PMC
PMC10877757
OpenAlex
W4389946632
Cited by
79
References
19
Citations by year
2026: 21 · 2025: 38 · 2024: 20
FWCI
2.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmacological Reviews (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • American Society for Pharmacology and Experimental Therapeutics
  • National Institutes of Health
  • National Institute on Aging (R01AG061805, RF1AG068629, R21AG075611)
  • National Institute on Drug Abuse (R01DA049267, R01DA017763)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
extracellular vesicles, liquid biopsy, neurological disorders, blood-based biomarkers, neurodegeneration, Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, major depressive disorder, substance use disorders, HIV-associated neurocognitive disorders, EV isolation, microglia, astrocytes, oligodendrocytes, pericytes, endothelial cells, non-invasive diagnosis
MeSH terms
Extracellular Vesicles, Liquid Biopsy, Alzheimer Disease, Depressive Disorder, Major, Major Depressive Disorder, Humans, Biomarkers

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