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Extracellular Vesicles of Alzheimer's Disease Patients as a Biomarker for Disease Progression.
Mol Neurobiol. 2020 Oct; 57(10):4156-4169.MN

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative brain pathology and the most common form of dementia. Evidence suggests that extracellular vesicles (EVs) containing cytokines and microRNA are involved in inflammation regulation. The current study aimed to explore a potential impact of AD patients' EVs on disease progression. Blood samples were collected after obtaining signed informed consent (No. 0462-14-RMB) from 42 AD patients at three stages of disease severity and from 19 healthy controls (HC). EV size and concentration were studied by nanotracking analysis. EV membrane antigens were defined by flow cytometry and Western blot; EV protein contents were screened by protein array; the miRNA content was screened by nanostring technology and validated by RT-PCR. HC and AD patients' EVs consisted of a mixture of small (< 100 nm) and larger vesicles. The myelin oligodendrocyte glycoprotein (MOG) expression on EVs correlated with disease severity. EVs of patients with moderate and severe AD had significantly higher levels of MOG, compared with mild AD patients. Levels of EVs expressing the axonal glycoprotein CD171 were significantly higher in severe AD patients than in HC. Increase in endothelial EVs was observed in AD patients. An above twofold increase was found in the content of inflammatory cytokines and > 50% decrease in growth factors in AD patients' EVs compared with HC-EVs. Levels of let-7g-5p, miR126-3p, miR142-3p, miR-146a-5p, and mir223-3p correlated with disease severity. Neural damage, specific miRNA downregulation, and inflammatory cytokine upregulation, found in patients' EVs, might be used as a biomarker reflecting AD severity.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Aharon A
Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. anataha@tlvmc.gov.il. Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel. anataha@tlvmc.gov.il. Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. anataha@tlvmc.gov.il.
Spector P
Cognitive Neurology Unit, Rambam Health Care Campus, Haifa, Israel.
Ahmad RS
Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel.
Horrany N
Cognitive Neurology Unit, Rambam Health Care Campus, Haifa, Israel.
Sabbach A
Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
Brenner B
Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel. Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Aharon-Peretz J
Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. Cognitive Neurology Unit, Rambam Health Care Campus, Haifa, Israel.

MeSH

AgedAlzheimer DiseaseBiomarkersCytokinesDisease ProgressionExosomesExtracellular VesiclesFemaleGene Expression RegulationHumansIntercellular Signaling Peptides and ProteinsMaleMicroRNAsMiddle AgedMyelin-Oligodendrocyte GlycoproteinNeuronsSeverity of Illness Index

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32676990

Citation

Aharon, Anat, et al. "Extracellular Vesicles of Alzheimer's Disease Patients as a Biomarker for Disease Progression." Molecular Neurobiology, vol. 57, no. 10, 2020, pp. 4156-4169.
Aharon A, Spector P, Ahmad RS, et al. Extracellular Vesicles of Alzheimer's Disease Patients as a Biomarker for Disease Progression. Mol Neurobiol. 2020;57(10):4156-4169.
Aharon, A., Spector, P., Ahmad, R. S., Horrany, N., Sabbach, A., Brenner, B., & Aharon-Peretz, J. (2020). Extracellular Vesicles of Alzheimer's Disease Patients as a Biomarker for Disease Progression. Molecular Neurobiology, 57(10), 4156-4169. https://doi.org/10.1007/s12035-020-02013-1
Aharon A, et al. Extracellular Vesicles of Alzheimer's Disease Patients as a Biomarker for Disease Progression. Mol Neurobiol. 2020;57(10):4156-4169. PubMed PMID: 32676990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extracellular Vesicles of Alzheimer's Disease Patients as a Biomarker for Disease Progression. AU - Aharon,Anat, AU - Spector,Polina, AU - Ahmad,Rawan Sayed, AU - Horrany,Nizar, AU - Sabbach,Annie, AU - Brenner,Benjamin, AU - Aharon-Peretz,Judith, Y1 - 2020/07/17/ PY - 2020/06/13/received PY - 2020/07/08/accepted PY - 2020/7/18/pubmed PY - 2021/6/10/medline PY - 2020/7/18/entrez KW - Alzheimer’s disease (AD) KW - Cytokines KW - Extracellular vesicles (EVs) KW - MicroRNA (miRNA) SP - 4156 EP - 4169 JF - Molecular neurobiology JO - Mol Neurobiol VL - 57 IS - 10 N2 - Alzheimer's disease (AD) is a progressive neurodegenerative brain pathology and the most common form of dementia. Evidence suggests that extracellular vesicles (EVs) containing cytokines and microRNA are involved in inflammation regulation. The current study aimed to explore a potential impact of AD patients' EVs on disease progression. Blood samples were collected after obtaining signed informed consent (No. 0462-14-RMB) from 42 AD patients at three stages of disease severity and from 19 healthy controls (HC). EV size and concentration were studied by nanotracking analysis. EV membrane antigens were defined by flow cytometry and Western blot; EV protein contents were screened by protein array; the miRNA content was screened by nanostring technology and validated by RT-PCR. HC and AD patients' EVs consisted of a mixture of small (< 100 nm) and larger vesicles. The myelin oligodendrocyte glycoprotein (MOG) expression on EVs correlated with disease severity. EVs of patients with moderate and severe AD had significantly higher levels of MOG, compared with mild AD patients. Levels of EVs expressing the axonal glycoprotein CD171 were significantly higher in severe AD patients than in HC. Increase in endothelial EVs was observed in AD patients. An above twofold increase was found in the content of inflammatory cytokines and > 50% decrease in growth factors in AD patients' EVs compared with HC-EVs. Levels of let-7g-5p, miR126-3p, miR142-3p, miR-146a-5p, and mir223-3p correlated with disease severity. Neural damage, specific miRNA downregulation, and inflammatory cytokine upregulation, found in patients' EVs, might be used as a biomarker reflecting AD severity. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/32676990/Extracellular_Vesicles_of_Alzheimer's_Disease_Patients_as_a_Biomarker_for_Disease_Progression_ DB - PRIME DP - Unbound Medicine ER -