A potential function for neuronal exosomes: Sequestering intracerebral amyloid-β peptide
A potential function for neuronal exosomes: Sequestering intracerebral amyloid-β peptide
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DOI：
10.1016/j.febslet.2014.11.027
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发表时间：
2015-01-02
期刊：
影响因子：
3.5
通讯作者：
Igarashi, Yasuyuki
中科院分区：
文献类型：
--
作者：
Yuyama, Kohei;Sun, Hui;Igarashi, Yasuyuki
脑淀粉样蛋白β肽（A β）的升高与阿尔茨海默病（AD）的发病机制有关。我们证实了食蟹猴和APP转基因小鼠脑脊液中存在外泌体相关的A β。老龄动物脑脊液中外泌体相关A β的水平明显下降。我们还确定神经元外泌体，而不是胶质外泌体，具有丰富的鞘糖脂并能捕获A β。将神经元外泌体输注到APP转基因小鼠的大脑中，可以减少A β和淀粉样蛋白沉积，这与之前关于神经母细胞瘤来源的外泌体的报道相似。这些发现强调了神经元外泌体在A β清除中的作用，并表明它们的下调可能与Ab积累有关，并最终导致AD病理的发展。(C) 2014年欧洲生化学会联合会。Elsevier B.V.版权所有。
Elevated amyloid-beta peptide (A beta) in brain contributes to Alzheimer's disease (AD) pathogenesis. We demonstrated the presence of exosome-associated A beta in the cerebrospinal fluid (CSF) of cynomolgus monkeys and APP transgenic mice. The levels of exosome-associated A beta notably decreased in the CSF of aging animals. We also determined that neuronal exosomes, but not glial exosomes, had abundant glycosphingolipids and could capture A beta. Infusion of neuronal exosomes into brains of APP transgenic mice decreased A beta and amyloid depositions, similarly to what reported previously on neuroblastoma-derived exosomes. These findings highlight the role of neuronal exosomes in A beta clearance, and suggest that their downregulation might relate to Ab accumulation and, ultimately, the development of AD pathology. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.