阿尔茨海默病临床亚型的粉样β纤维的结构变化
Wei Qiang1, Wai-Ming Yau1, Jun-Xia Lu1
1Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature
|January 5, 2017
概括
阿尔茨海默病的粉样β纤维结构因临床亚型而异. 一个特定的粉样β40纤维结构与典型和PCA形式相关,而快速渐进的形式显示出更多的结构多样性.
科学领域:
- 神经科学
- 生物化学
- 结构生物学
背景情况:
- 粉样β (Aβ) 聚成纤维素是阿尔茨海默病 (AD) 发病的关键.
- Aβ纤维结构多态,可能与阿尔茨海默病的临床表型相关,类似于子菌株.
研究的目的:
- 调查粉样β纤维的结构变化与不同的阿尔茨海默病表型之间的相关性.
- 为了比较典型的AD (t-AD),快速进展的AD (r-AD) 和后皮层缩的AD (PCA-AD) 的Aβ纤维结构.
主要方法:
- 使用固态核磁共振 (ssNMR) 来分析Aβ40和Aβ42纤维结构.
- 纤维是由阿尔茨海默氏症大脑皮质提取物的种子生长制备的.
- 分析了来自18个代表不同AD亚型的37个皮质组织样本.
主要成果:
- 在t-AD和PCA-AD样本中发现了一个单一的主导的Aβ40纤维结构.
- 来自r-AD样本的Aβ40纤维显示出更多的额外结构.
- 在所有患者类别中,Aβ42纤维素具有结构异质性,至少有两个主要结构.
结论:
- 与典型和PCA-AD相关的是特定的主导的Aβ40纤维结构.
- 快速进展的AD可能涉及额外的粉样β纤维结构.
- 在阿尔茨海默病的大脑组织中存在Aβ40和Aβ42聚合物的定性差异.
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