Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
Cell. 2013 Sep 12;154(6):1257-68. doi: 10.1016/j.cell.2013.08.035.
In vitro, β-amyloid (Aβ) peptides form polymorphic fibrils, with molecular structures that depend on growth conditions, plus various oligomeric and protofibrillar aggregates. Here, we investigate structures of human brain-derived Aβ fibrils, using seeded fibril growth from brain extract and data from solid-state nuclear magnetic resonance and electron microscopy. Experiments on tissue from two Alzheimer's disease (AD) patients with distinct clinical histories showed a single predominant 40 residue Aβ (Aβ40) fibril structure in each patient; however, the structures were different from one another. A molecular structural model developed for Aβ40 fibrils from one patient reveals features that distinguish in-vivo- from in-vitro-produced fibrils. The data suggest that fibrils in the brain may spread from a single nucleation site, that structural variations may correlate with variations in AD, and that structure-specific amyloid imaging agents may be an important future goal.
在体外，β-淀粉样蛋白（Aβ）肽形成多态性纤维，其分子结构取决于生长条件，以及各种寡聚体和原纤维聚集体。在这里，我们使用脑提取物中的种子纤维生长以及固态核磁共振和电子显微镜的数据来研究人脑源性 Aβ纤维的结构。对来自具有不同临床病史的两位阿尔茨海默病（AD）患者的组织的实验表明，每个患者中都存在单一的主要 40 个残基 Aβ（Aβ40）纤维结构；然而，这些结构彼此不同。为一位患者的 Aβ40 纤维建立的分子结构模型揭示了区分体内和体外产生纤维的特征。这些数据表明，大脑中的纤维可能从单个成核位点传播，结构变化可能与 AD 的变化相关，并且结构特异性淀粉样蛋白成像剂可能是未来的一个重要目标。
