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

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Platelet‐derived extracellular vesicles are increased in sera of Alzheimer's disease patients, as revealed by Tim4‐based assays
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-12-20 , DOI: 10.1002/2211-5463.13068
Haruki Odaka ₁ , Keiko Hiemori ₁ , Asako Shimoda ₂ , Kazunari Akiyoshi ₂ , Hiroaki Tateno ₁

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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.

中文翻译：

基于 Tim4 的检测结果显示，阿尔茨海默病患者血清中血小板衍生的细胞外囊泡增加

阿尔茨海默病（AD）是最常见的痴呆症，其特征是β-淀粉样斑块的积聚和神经原纤维缠结的形成。细胞外囊泡 (EVs) 是被脂质双层膜包围的小囊泡，可能与 AD 的进展有关。聚糖是 EV 的重要组成部分，我们假设 EV 聚糖可能反映各种疾病的病理状况。在这里，我们使用凝集素微阵列对从三名 AD 患者 (AP) 与三名健康供体 (HD) 的血清制备的 EV 进行了聚糖分析。观察到不同的聚糖谱。与 HD 衍生的 EV 相比，甘露糖结合凝集素对 AP 衍生的 EV 表现出明显更高的信号。使用甘露糖结合凝集素 (rPALa) 的凝集素印迹显示，仅在 AP 衍生的 EV 中存在约 80 kDa 的单个蛋白质条带。LC-MS/MS 分析将 rPALa 沉淀的蛋白质条带鉴定为 CD61，这是血小板衍生外泌体 (P-Exo) 的标志物。使用 Tim4 特异性检测 EV 上的磷脂酰丝氨酸和针对 P-Exo 标志物（CD61、CD41、CD63 和 CD9）的抗体进行的夹心分析显示，AP 血清中的 P-Exo 显着升高。n = 16) 相对于年龄和性别匹配的 HD ( n = 16)。Tim4-αCD63 在区分 AP 与 HD 的曲线下面积（0.957）中显示出最高值，这应该有助于更好地了解 AD 病理学，并可能有助于开发一种新的 AD 诊断方法。

更新日期：2020-12-20

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