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Characterization of Serum Exosomes from a Transgenic Mouse Model of Alzheimer's Disease.
Current Alzheimer Research ( IF 2.1 ) Pub Date : 2019-01-01 , DOI: 10.2174/1567205016666190321155422
Hector Rosas-Hernandez 1 , Elvis Cuevas 1 , James B Raymick 1 , Bonnie L Robinson 1 , Syed F Ali 1 , Joseph Hanig 2 , Sumit Sarkar 1
Affiliation  

BACKGROUND Alzheimer's Disease (AD) is the most common type of dementia characterized by amyloid plaques containing Amyloid Beta (Aβ) peptides and neurofibrillary tangles containing tau protein. In addition to neuronal loss, Cerebral Amyloid Angiopathy (CAA) commonly occurs in AD. CAA is characterized by Aβ deposition in brain microvessels. Recent studies have suggested that exosomes (cell-derived vesicles containing a diverse cargo) may be involved in the pathogenesis of AD. OBJECTIVE Isolate and characterize brain-derived exosomes from a transgenic mouse model of AD that presents CAA. METHODS Exosomes were isolated from serum obtained from 13-month-old wild type and AD transgenic female mice using an exosome precipitation solution. Characterization of exosomal proteins was performed by western blots and dot blots. RESULTS Serum exosomes were increased in transgenic mice compared to wild types as determined by increased levels of the exosome markers flotillin and alix. High levels of neuronal markers were found in exosomes, without any difference any between the 2 groups. Markers for endothelial-derived exosomes were decreased in the transgenic model, while astrocytic-derived exosomes were increased. Exosome characterization showed increased levels of oligomeric Aβ and oligomeric and monomeric forms tau on the transgenic animals. Levels of amyloid precursor protein were also increased. In addition, pathological and phosphorylated forms of tau were detected, but no difference was observed between the groups. CONCLUSION These data suggest that monomeric and oligomeric forms of Aβ and tau are secreted into serum via brain exosomes, most likely derived from astrocytes in the transgenic mouse model of AD with CAA. Studies on the implication of this event in the propagation of AD are underway.

中文翻译:

从阿尔茨海默氏病的转基因小鼠模型血清外来体的表征。

背景技术阿尔茨海默氏病(AD)是最常见的痴呆类型,其特征在于含有淀粉样β(Aβ)肽的淀粉样斑块和含有tau蛋白的神经原纤维缠结。除神经元丢失外,脑淀粉样血管病(CAA)通常在AD中发生。CAA的特征是脑微血管中的Aβ沉积。最近的研究表明,外泌体(细胞来源的囊泡中含有多种物质)可能与AD的发病有关。目的从呈递CAA的AD转基因小鼠模型中分离并鉴定脑源性外泌体。方法使用外泌体沉淀溶液从13个月大的野生型和AD转基因雌性小鼠的血清中分离外泌体。通过蛋白质印迹和斑点印迹对外泌体蛋白进行表征。结果转基因小鼠的血清外泌体与野生型相比有所增加,这是通过外泌体标志物弗洛林和a的水平升高确定的。在外泌体中发现了高水平的神经元标记物,两组之间没有任何差异。转基因模型中内皮源性外泌体的标记减少,而星形细胞源性外泌体的标记增加。外来体的表征显示在转基因动物上寡聚Aβ以及寡聚和单体形式tau的水平升高。淀粉样蛋白前体蛋白的水平也增加了。另外,检测到tau的病理形式和磷酸化形式,但两组之间未观察到差异。结论这些数据表明Aβ和tau的单体和寡聚形式通过脑外泌体分泌到血清中,最有可能源自具有CAA的AD转基因小鼠模型中的星形胶质细胞。有关此事件对AD传播的影响的研究正在进行中。
更新日期:2019-11-01
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