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Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays

Alzheimer's disease (AD) is the most common form of dementia, characterized by the accumulation of β‐amyloid plaques and the formation of neurofibrillary tangles. Extracellular vesicles (EVs) are small vesicles surrounded by a lipid bilayer membrane, which may be involved in the progression of...

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Autores principales: Odaka, Haruki, Hiemori, Keiko, Shimoda, Asako, Akiyoshi, Kazunari, Tateno, Hiroaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931225/
https://www.ncbi.nlm.nih.gov/pubmed/33345458
http://dx.doi.org/10.1002/2211-5463.13068
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author Odaka, Haruki
Hiemori, Keiko
Shimoda, Asako
Akiyoshi, Kazunari
Tateno, Hiroaki
author_facet Odaka, Haruki
Hiemori, Keiko
Shimoda, Asako
Akiyoshi, Kazunari
Tateno, Hiroaki
author_sort Odaka, Haruki
collection PubMed
description Alzheimer's disease (AD) is the most common form of dementia, characterized by the accumulation of β‐amyloid plaques and the formation of neurofibrillary tangles. Extracellular vesicles (EVs) are small vesicles surrounded by a lipid bilayer membrane, which may be involved in the progression of AD. Glycans are essential building blocks of EVs, and we hypothesized that EV glycans may reflect pathological conditions of various diseases. Here, we performed glycan profiling of EVs prepared from sera of three AD patients (APs) compared to three healthy donors (HDs) using lectin microarray. Distinct glycan profiles were observed. Mannose‐binding lectins exhibited significantly higher signals for AP‐derived EVs than HD‐derived EVs. Lectin blotting using mannose‐binding lectin (rPALa) showed a single protein band at ~ 80 kDa exclusively in AP‐derived EVs. LC‐MS/MS analysis identified a protein band precipitated by rPALa as CD61, a marker of platelet‐derived exosomes (P‐Exo). Sandwich assays using Tim4 with specificity for phosphatidylserine on EVs and antibodies against P‐Exo markers (CD61, CD41, CD63, and CD9) revealed that P‐Exo is significantly elevated in sera of APs (n = 16) relative to age‐ and sex‐matched HDs (n = 16). Tim4‐αCD63 showed the highest value for the area under the curve (0.957) for discriminating APs from HDs, which should lead to a better understanding of AD pathology and may facilitate the development of a novel diagnostic method for AD.
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spelling pubmed-79312252021-03-15 Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays Odaka, Haruki Hiemori, Keiko Shimoda, Asako Akiyoshi, Kazunari Tateno, Hiroaki FEBS Open Bio Research Articles Alzheimer's disease (AD) is the most common form of dementia, characterized by the accumulation of β‐amyloid plaques and the formation of neurofibrillary tangles. Extracellular vesicles (EVs) are small vesicles surrounded by a lipid bilayer membrane, which may be involved in the progression of AD. Glycans are essential building blocks of EVs, and we hypothesized that EV glycans may reflect pathological conditions of various diseases. Here, we performed glycan profiling of EVs prepared from sera of three AD patients (APs) compared to three healthy donors (HDs) using lectin microarray. Distinct glycan profiles were observed. Mannose‐binding lectins exhibited significantly higher signals for AP‐derived EVs than HD‐derived EVs. Lectin blotting using mannose‐binding lectin (rPALa) showed a single protein band at ~ 80 kDa exclusively in AP‐derived EVs. LC‐MS/MS analysis identified a protein band precipitated by rPALa as CD61, a marker of platelet‐derived exosomes (P‐Exo). Sandwich assays using Tim4 with specificity for phosphatidylserine on EVs and antibodies against P‐Exo markers (CD61, CD41, CD63, and CD9) revealed that P‐Exo is significantly elevated in sera of APs (n = 16) relative to age‐ and sex‐matched HDs (n = 16). Tim4‐αCD63 showed the highest value for the area under the curve (0.957) for discriminating APs from HDs, which should lead to a better understanding of AD pathology and may facilitate the development of a novel diagnostic method for AD. John Wiley and Sons Inc. 2021-02-03 /pmc/articles/PMC7931225/ /pubmed/33345458 http://dx.doi.org/10.1002/2211-5463.13068 Text en © 2020 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Odaka, Haruki
Hiemori, Keiko
Shimoda, Asako
Akiyoshi, Kazunari
Tateno, Hiroaki
Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays
title Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays
title_full Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays
title_fullStr Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays
title_full_unstemmed Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays
title_short Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays
title_sort platelet‐derived extracellular vesicles are increased in sera of alzheimer's disease patients, as revealed by tim4‐based assays
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931225/
https://www.ncbi.nlm.nih.gov/pubmed/33345458
http://dx.doi.org/10.1002/2211-5463.13068
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