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Extracellular Vesicle as a Source of Alzheimer's Biomarkers: Opportunities and Challenges.
Int J Mol Sci. 2019 Apr 08; 20(7)IJ

Abstract

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aβ) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry.

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Authors+Show Affiliations

Lee S
Department of Anatomy, College of Medicine, Inha University, Incheon 22212, Korea. lees@inha.ac.kr. Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Korea. lees@inha.ac.kr.
Mankhong S
Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Korea. sakulratkulrat@gmail.com. Department of Pharmacology, College of Medicine, Inha University, Incheon 22212, Korea. sakulratkulrat@gmail.com.
Kang JH
Hypoxia-related Disease Research Center, College of Medicine, Inha University, Incheon 22212, Korea. johykang@inha.ac.kr. Department of Pharmacology, College of Medicine, Inha University, Incheon 22212, Korea. johykang@inha.ac.kr.

MeSH

Alzheimer DiseaseAnimalsBiomarkersCentral Nervous SystemExosomesExtracellular VesiclesHumans

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30965555

Citation

Lee, Seongju, et al. "Extracellular Vesicle as a Source of Alzheimer's Biomarkers: Opportunities and Challenges." International Journal of Molecular Sciences, vol. 20, no. 7, 2019.
Lee S, Mankhong S, Kang JH. Extracellular Vesicle as a Source of Alzheimer's Biomarkers: Opportunities and Challenges. Int J Mol Sci. 2019;20(7).
Lee, S., Mankhong, S., & Kang, J. H. (2019). Extracellular Vesicle as a Source of Alzheimer's Biomarkers: Opportunities and Challenges. International Journal of Molecular Sciences, 20(7). https://doi.org/10.3390/ijms20071728
Lee S, Mankhong S, Kang JH. Extracellular Vesicle as a Source of Alzheimer's Biomarkers: Opportunities and Challenges. Int J Mol Sci. 2019 Apr 8;20(7) PubMed PMID: 30965555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular Vesicle as a Source of Alzheimer's Biomarkers: Opportunities and Challenges. AU - Lee,Seongju, AU - Mankhong,Sakulrat, AU - Kang,Ju-Hee, Y1 - 2019/04/08/ PY - 2019/03/03/received PY - 2019/04/01/revised PY - 2019/04/01/accepted PY - 2019/4/11/entrez PY - 2019/4/11/pubmed PY - 2019/7/28/medline KW - Alzheimer’s disease KW - biomarker KW - central nervous system KW - exosome KW - extracellular vesicles KW - standardization JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 7 N2 - Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease characterized by memory decline and cognitive dysfunction. Although the primary causes of AD are not clear, it is widely accepted that the accumulation of amyloid beta (Aβ) and consecutive hyper-phosphorylation of tau, synaptic loss, oxidative stress and neuronal death might play a vital role in AD pathogenesis. Recently, it has been widely suggested that extracellular vesicles (EVs), which are released from virtually all cell types, are a mediator in regulating AD pathogenesis. Clinical evidence for the diagnostic performance of EV-associated biomarkers, particularly exosome biomarkers in the blood, is also emerging. In this review, we briefly introduce the biological function of EVs in the central nervous system and discuss the roles of EVs in AD pathogenesis. In particular, the roles of EVs associated with autophagy and lysosomal degradation systems in AD proteinopathy and in disease propagation are discussed. Next, we summarize candidates for biochemical AD biomarkers in EVs, including proteins and miRNAs. The accumulating data brings hope that the application of EVs will be helpful for early diagnostics and the identification of new therapeutic targets for AD. However, at the same time, there are several challenges in developing valid EV biomarkers. We highlight considerations for the development of AD biomarkers from circulating EVs, which includes the standardization of pre-analytical sources of variability, yield and purity of isolated EVs and quantification of EV biomarkers. The development of valid EV AD biomarkers may be facilitated by collaboration between investigators and the industry. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/30965555/Extracellular_Vesicle_as_a_Source_of_Alzheimer's_Biomarkers:_Opportunities_and_Challenges_ DB - PRIME DP - Unbound Medicine ER -