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MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer's Disease.
Cells. 2020 06 10; 9(6)C

Abstract

Small extracellular vesicles (EVs) are able to pass from the central nervous system (CNS) into peripheral blood and contain molecule markers of their parental origin. The aim of our study was to isolate and characterize total and neural-derived small EVs (NDEVs) and their micro RNA (miRNA) cargo in Alzheimer's disease (AD) patients. Small NDEVs were isolated from plasma in a population consisting of 40 AD patients and 40 healthy subjects (CTRLs) using high throughput Advanced TaqMan miRNA OpenArrays®, which enables the simultaneous determination of 754 miRNAs. MiR-23a-3p, miR-223-3p, miR-100-3p and miR-190-5p showed a significant dysregulation in small NDEVs from AD patients as compared with controls (1.16 ± 0.49 versus 7.54 ± 2.5, p = 0.026; 9.32 ± 2.27 versus 0.66 ± 0.18, p <0.0001; 0.069 ± 0.01 versus 0.5 ± 0.1, p < 0.0001 and 2.9 ± 1.2 versus 1.93 ± 0.9, p < 0.05, respectively). A further validation analysis confirmed that miR-23a-3p, miR-223-3p and miR-190a-5p levels in small NDEVs from AD patients were significantly upregulated as compared with controls (p = 0.008; p = 0.016; p = 0.003, respectively) whereas miR-100-3p levels were significantly downregulated (p = 0.008). This is the first study that carries out the comparison between total plasma small EV population and NDEVs, demonstrating the presence of a specific AD NDEV miRNA signature.

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Authors+Show Affiliations

Serpente M
Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, 20122 Milan, Italy.
Fenoglio C
Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, 20122 Milan, Italy.
D'Anca M
Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of Milan, 20122 Milan, Italy.
Arcaro M
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Sorrentino F
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy. Department of Biomedical, Surgical and Dental Sciences, Dino Ferrari Center, CRC Molecular Basis of Neuro-Psycho-Geriatrics Diseases, University of Milan, 20122 Milan, Italy.
Visconte C
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Arighi A
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Fumagalli GG
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Porretti L
Flow Cytometry Service, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Cattaneo A
Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Ciani M
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
Zanardini R
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
Benussi L
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
Ghidoni R
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy.
Scarpini E
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy. Department of Biomedical, Surgical and Dental Sciences, Dino Ferrari Center, CRC Molecular Basis of Neuro-Psycho-Geriatrics Diseases, University of Milan, 20122 Milan, Italy.
Galimberti D
Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy. Department of Biomedical, Surgical and Dental Sciences, Dino Ferrari Center, CRC Molecular Basis of Neuro-Psycho-Geriatrics Diseases, University of Milan, 20122 Milan, Italy.

MeSH

AgedAlzheimer DiseaseCase-Control StudiesExtracellular VesiclesFemaleGenetic ProfileHumansMaleMicroRNAsMiddle Aged

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32531989

Citation

Serpente, Maria, et al. "MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles From Patients With Alzheimer's Disease." Cells, vol. 9, no. 6, 2020.
Serpente M, Fenoglio C, D'Anca M, et al. MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer's Disease. Cells. 2020;9(6).
Serpente, M., Fenoglio, C., D'Anca, M., Arcaro, M., Sorrentino, F., Visconte, C., Arighi, A., Fumagalli, G. G., Porretti, L., Cattaneo, A., Ciani, M., Zanardini, R., Benussi, L., Ghidoni, R., Scarpini, E., & Galimberti, D. (2020). MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer's Disease. Cells, 9(6). https://doi.org/10.3390/cells9061443
Serpente M, et al. MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles From Patients With Alzheimer's Disease. Cells. 2020 06 10;9(6) PubMed PMID: 32531989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiRNA Profiling in Plasma Neural-Derived Small Extracellular Vesicles from Patients with Alzheimer's Disease. AU - Serpente,Maria, AU - Fenoglio,Chiara, AU - D'Anca,Marianna, AU - Arcaro,Marina, AU - Sorrentino,Federica, AU - Visconte,Caterina, AU - Arighi,Andrea, AU - Fumagalli,Giorgio G, AU - Porretti,Laura, AU - Cattaneo,Alessandra, AU - Ciani,Miriam, AU - Zanardini,Roberta, AU - Benussi,Luisa, AU - Ghidoni,Roberta, AU - Scarpini,Elio, AU - Galimberti,Daniela, Y1 - 2020/06/10/ PY - 2020/04/29/received PY - 2020/06/04/revised PY - 2020/06/08/accepted PY - 2020/6/14/entrez PY - 2020/6/14/pubmed PY - 2021/3/19/medline KW - Alzheimer’s disease KW - extracellular vesicles (EVs) KW - microRNA KW - neural-derived extracellular vesicles (NDEVs) JF - Cells JO - Cells VL - 9 IS - 6 N2 - Small extracellular vesicles (EVs) are able to pass from the central nervous system (CNS) into peripheral blood and contain molecule markers of their parental origin. The aim of our study was to isolate and characterize total and neural-derived small EVs (NDEVs) and their micro RNA (miRNA) cargo in Alzheimer's disease (AD) patients. Small NDEVs were isolated from plasma in a population consisting of 40 AD patients and 40 healthy subjects (CTRLs) using high throughput Advanced TaqMan miRNA OpenArrays®, which enables the simultaneous determination of 754 miRNAs. MiR-23a-3p, miR-223-3p, miR-100-3p and miR-190-5p showed a significant dysregulation in small NDEVs from AD patients as compared with controls (1.16 ± 0.49 versus 7.54 ± 2.5, p = 0.026; 9.32 ± 2.27 versus 0.66 ± 0.18, p <0.0001; 0.069 ± 0.01 versus 0.5 ± 0.1, p < 0.0001 and 2.9 ± 1.2 versus 1.93 ± 0.9, p < 0.05, respectively). A further validation analysis confirmed that miR-23a-3p, miR-223-3p and miR-190a-5p levels in small NDEVs from AD patients were significantly upregulated as compared with controls (p = 0.008; p = 0.016; p = 0.003, respectively) whereas miR-100-3p levels were significantly downregulated (p = 0.008). This is the first study that carries out the comparison between total plasma small EV population and NDEVs, demonstrating the presence of a specific AD NDEV miRNA signature. SN - 2073-4409 UR - https://www.unboundmedicine.com/medline/citation/32531989/MiRNA_Profiling_in_Plasma_Neural_Derived_Small_Extracellular_Vesicles_from_Patients_with_Alzheimer's_Disease_ DB - PRIME DP - Unbound Medicine ER -