Institute for Bioengineering of Catalonia, Baldiri Reixac 15, Barcelona, Spain.
Bioconjug Chem. 2012 Jan 18;23(1):27-32. doi: 10.1021/bc200077s. Epub 2011 Dec 12.
Amyloid-β protein (Aβ) aggregation into amyloid fibrils is central to the origin and development of Alzheimer's disease (AD), yet this highly complex process is poorly understood at the molecular level. Extensive studies have shown that Aβ fibril growth occurs through fibril elongation, whereby soluble molecules add to the fibril ends. Nevertheless, fibril morphology strongly depends on aggregation conditions. For example, at high ionic strength, Aβ fibrils laterally associate into bundles. To further study the mechanisms leading to fibril growth, we developed a single-fibril growth assay based on differential labeling of two Aβ42 variants with gold nanoparticles. We used this assay to study Aβ42 fibril growth under different conditions and observed that bundle formation is preceded by lateral interaction of soluble Aβ42 molecules with pre-existing fibrils. Based on this data, we propose template-assisted lateral fibril growth as an additional mechanism to elongation for Aβ42 fibril growth.
淀粉样β蛋白（Aβ）聚集成淀粉样纤维是阿尔茨海默病（AD）的起源和发展的核心，但这一高度复杂的过程在分子水平上还了解甚少。大量研究表明，Aβ纤维的生长是通过纤维的延伸来实现的，即可溶性分子添加到纤维的末端。然而，纤维形态强烈依赖于聚集条件。例如，在高离子强度下，Aβ纤维侧向聚集形成束。为了进一步研究导致纤维生长的机制，我们开发了一种基于两种 Aβ42 变体用金纳米粒子进行差异标记的单纤维生长测定法。我们使用该测定法在不同条件下研究 Aβ42 纤维的生长，观察到束形成之前可溶性 Aβ42 分子与预先存在的纤维发生侧向相互作用。基于这些数据，我们提出模板辅助的侧向纤维生长作为 Aβ42 纤维生长的伸长的另一种机制。
