The aggregation of amyloid-β (Aβ) is believed to be foundational to the pathogenesis of Alzheimer's disease (AD). In vitro aggregation kinetics have been shown to correlate with rates of disease progression in both AD patients and animal models, thus proving to be a useful metric for testing Aβ-targeted therapeutics. Here we present evidence of cobalt(III) Schiff base complex ([Co(acetylacetonate)(NH₃)₂]Cl; Co(III)-sb) modulation of Aβ aggregation kinetics by a variety of complementary techniques. These include Thioflavin T (ThT) fluorescence, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), and atomic force microscopy (AFM). Our data was fitted to kinetic rate laws using a mathematical model developed by Knowles et al. in order to extract mechanistic information about the effect of Co(III)-sb on aggregation kinetics. Our analysis revealed that Co(III)-sb alters Aβ aggregation by decreasing the polymerization rate and increasing the nucleation rate, suggesting that Co(III)-sb causes Aβ to rapidly stabilize oligomeric species with reduced elongation into mature fibrils. This result was corroborated by TEM and AFM of Aβ aggregates in vitro. We also demonstrate that Aβ aggregate mixtures produced in the presence of Co(III)-sb exhibit decreased cytotoxicity compared to untreated samples.

淀粉样β（Aβ）的聚集被认为是阿尔茨海默氏病（AD）发病机理的基础。在AD患者和动物模型中，体外聚集动力学已经显示出与疾病进展速率相关，因此被证明是用于测试靶向Aβ的治疗剂的有用度量。在这里，我们提供钴（III）Schiff碱配合物（[[Co（乙酰丙酮））（NH ₃）₂] Cl; 通过多种互补技术对Aβ聚集动力学的Co（III）-sb）调节。这些包括硫黄素T（ThT）荧光，圆二色性（CD）光谱，透射电子显微镜（TEM）和原子力显微镜（AFM）。我们使用诺尔斯（Knowles）等人开发的数学模型将数据拟合为动量定律。为了提取有关Co（III）-sb对聚集动力学影响的机理信息。我们的分析表明，Co（III）-sb通过降低聚合速率和增加成核速率来改变Aβ聚集，这表明Co（III）-sb导致Aβ快速稳定寡聚物种，而伸长率降低到成熟的原纤维。体外Aβ聚集体的TEM和AFM证实了这一结果。我们还证明，与未处理的样品相比，在Co（III）-sb存在下产生的Aβ聚集混合物表现出降低的细胞毒性。