Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays. Issue 3 (3rd February 2021)

• Record Type: Journal Article
• Authors: Odaka, Haruki; Hiemori, Keiko; Shimoda, Asako; Akiyoshi, Kazunari; Tateno, Hiroaki
• Is Part Of: FEBS open bio. Volume 11:Issue 3(2021)
• Page Start: 741
• Page End: 752
• Publication Date: 2021-02-03
• Subjects: Alzheimer's disease -- extracellular vesicles -- lectin microarray -- platelet -- sandwich assay -- Tim4; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13068
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : 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. Abstract : Glycan profiling and LC‐MS/MS analysis revealed upregulation of exosomes containing a platelet marker CD61 in sera of Alzheimer's patients (APs) relative to healthy donors (HDs). Quantitative analysis using Tim4‐based sandwich assays provided further evidence that platelet‐derived exosomes (P‐Exo) are increased in sera of APs. Sandwich assays to detect P‐Exo showed high specificity and sensitivity to discriminate APs from HDs.