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  • Review Article
  • Published:

Extracellular vesicles in neurodegenerative disease — pathogenesis to biomarkers

Key Points

  • Extracellular vesicles (EVs) are secreted by cells of the CNS

  • EVs can be exosomes, microvesicles or apoptotic bodies, and their cargo reflects their cellular origin

  • EVs are implicated in neurodegenerative disease according to the prion-like hypothesis of propagation

  • RNA and protein associated with EVs from the cerebrospinal fluid (CSF) and serum show promise as early biomarkers for some neurodegenerative diseases, but require validation

  • Identification of robust markers of the most relevant — but relatively low-abudance — EVs in the CSF and blood is a major ongoing challenge

  • Focus is needed on the development of high-yield EV extraction methods that are ultimately applicable to routine clinical use

Abstract

To develop effective disease-modifying therapies for neurodegenerative diseases, reliable markers of diagnosis, disease activity and progression are a research priority. The fact that neurodegenerative pathology is primarily associated with distinct subsets of cells in discrete areas of the CNS makes the identification of relevant biomarker molecules a challenge. The trafficking of macromolecules from the CNS to the cerebrospinal fluid and blood, mediated by extracellular vesicles (EVs), presents a promising source of CNS-specific biomarkers. EVs are released by almost all cell types and carry a cargo of protein and nucleic acid that varies according to the cell of origin. EV output changes with cell status and reflects intracellular events, so surface marker expression can be used to identify the cell type from which EVs originate. EVs could, therefore, provide an enriched pool of information about core neuropathogenic, cell-specific processes. This Review examines the current knowledge of the biology and function of EVs, discusses the evidence for their involvement in the pathogenesis of neurodegenerative diseases, and considers their potential as biomarkers of disease.

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Figure 1: EV biogenesis and intercellular interactions.
Figure 2: Prion-like propagation of protein aggregates.

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A.G.T. and E.G. researched data for the article. A.G.T., E.G., S.M.H.-A., M.J.W and M.R.T. wrote the article. All authors made substantial contributions to discussion of the content and reviewed and/or edited the article before submission.

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Correspondence to Matthew J. Wood or Martin R. Turner.

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M.J.W. and S.A. have filed for and been granted patent applications in relation to extracellular vesicles. The other authors declare no competing interests.

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Thompson, A., Gray, E., Heman-Ackah, S. et al. Extracellular vesicles in neurodegenerative disease — pathogenesis to biomarkers. Nat Rev Neurol 12, 346–357 (2016). https://doi.org/10.1038/nrneurol.2016.68

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