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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Online Access: | https://doi.org/10.1002/2211-5463.13068 |
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doaj-5e37a2b6f8af47e688d8e7f61f0307c72021-03-04T10:35:45ZengWileyFEBS Open Bio2211-54632021-03-0111374175210.1002/2211-5463.13068Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assaysHaruki Odaka0Keiko Hiemori1Asako Shimoda2Kazunari Akiyoshi3Hiroaki Tateno4Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology Tsukuba JapanCellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology Tsukuba JapanDepartment of Polymer Chemistry Graduate School of Engineering Kyoto University JapanDepartment of Polymer Chemistry Graduate School of Engineering Kyoto University JapanCellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology Tsukuba JapanAlzheimer'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.https://doi.org/10.1002/2211-5463.13068Alzheimer’s diseaseextracellular vesicleslectin microarrayplateletsandwich assayTim4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Haruki Odaka Keiko Hiemori Asako Shimoda Kazunari Akiyoshi Hiroaki Tateno |
spellingShingle |
Haruki Odaka Keiko Hiemori Asako Shimoda Kazunari Akiyoshi Hiroaki Tateno Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays FEBS Open Bio Alzheimer’s disease extracellular vesicles lectin microarray platelet sandwich assay Tim4 |
author_facet |
Haruki Odaka Keiko Hiemori Asako Shimoda Kazunari Akiyoshi Hiroaki Tateno |
author_sort |
Haruki Odaka |
title |
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_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_sort |
platelet‐derived extracellular vesicles are increased in sera of alzheimer's disease patients, as revealed by tim4‐based assays |
publisher |
Wiley |
series |
FEBS Open Bio |
issn |
2211-5463 |
publishDate |
2021-03-01 |
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. |
topic |
Alzheimer’s disease extracellular vesicles lectin microarray platelet sandwich assay Tim4 |
url |
https://doi.org/10.1002/2211-5463.13068 |
work_keys_str_mv |
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