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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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General Research Article

积极的β-淀粉样蛋白疫苗接种会导致阿尔茨海默氏病小鼠模型的海马表观遗传学变化

卷 16, 期 9, 2019

页: [861 - 870] 页: 10

弟呕挨: 10.2174/1567205016666190827122009

价格: $65

摘要

背景：尽管有证据表明表观遗传修饰在阿尔茨海默氏病（AD）的病理生理级联中发挥作用，但针对淀粉样β（Aβ）的主动免疫疗法正在研究中，以预防或减缓AD的进展。迄今为止，尚未研究过Aβ活性疫苗对表观遗传标记的影响。 目的：本研究旨在建立基于免疫的免疫治疗与基于MER5101的疫苗（由在Th2偏置的佐剂中配制的Aβ1-15拷贝与7aa间隔子缀合的白喉类毒素载体蛋白组成）之间的关系。 APPswe / PS1dE9小鼠海马中的修饰。 方法：正如我们先前报道的那样，免疫疗法从小鼠10个月大时开始，并在14个月大时进行行为测试，然后处死小鼠以进一步分析其大脑。在这项附加研究中，使用定量免疫组织化学测定了DNA甲基化和羟甲基化以及DNA甲基转移酶3A（DNMT3A）的总体水平，并将其与我们先前分析的免疫诱导的AD相关神经病理学和认知变化进行了比较。 结果：主动免疫不会影响总体DNA甲基化水平，但会导致DNA羟甲基化和DNMT3A水平降低。与免疫无关，DNA甲基化和羟甲基化水平以及DNMT3A的水平与行为表现呈负相关，而Aβ病理学和突触标记与DNA甲基化水平不相关，但与DNA羟甲基化水平和DNMT3A呈正相关。 结论：我们的结果表明，主动Aβ疫苗接种对APPswe / PS1dE9小鼠海马表观基因组有重要影响，并表明DNA甲基化和羟甲基化可能与认知功能有关。

关键词: 阿尔茨海默氏病，淀粉样β蛋白，活性疫苗，表观遗传学，DNA甲基化，小鼠模型。

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