摘要
背景：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蛋白β（Aβ）肽和含有tau蛋白的神经原纤维缠结的淀粉样斑块。除神经元丢失外，脑淀粉样血管病（CAA）通常发生在AD中。 CAA的特征在于脑微血管中的Aβ沉积。最近的研究表明外泌体（含有不同载体的细胞衍生的囊泡）可能参与AD的发病机制。 目的：从呈递CAA的转基因小鼠AD模型中分离和表征来源于脑的外泌体。 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进行外来体蛋白质的表征。 结果：与野生型相比，转基因小鼠的血清外泌体增加，这可通过外泌体标记物flotillin和alix的水平增加来确定。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。内皮细胞衍生的外泌体标记在转基因模型中减少，而星形胶质细胞衍生的外泌体增加。外来体表征显示转基因动物上寡聚Aβ和寡聚和单体形式tau的水平增加。淀粉样蛋白前体蛋白的水平也增加。此外，检测到tau的病理和磷酸化形式，但两组之间未观察到差异。 结论：这些数据表明Aβ和tau的单体和寡聚体形式通过脑外泌体分泌到血清中，最可能来源于ADA转基因小鼠模型中的星形胶质细胞。关于该事件在AD传播中的意义的研究正在进行中。
关键词: 阿尔茨海默病，脑淀粉样血管病，外泌体，淀粉样蛋白β，tau，淀粉样蛋白前体蛋白。
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