Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK.
Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.
J Neurochem. 2022 Feb;160(4):434-453. doi: 10.1111/jnc.15538. Epub 2021 Nov 24.
Although controversial, the amyloid cascade hypothesis remains central to the Alzheimer's disease (AD) field and posits amyloid-beta (Aβ) as the central factor initiating disease onset. In recent years, there has been an increase in emphasis on studying the role of low molecular weight aggregates, such as oligomers, which are suggested to be more neurotoxic than fibrillary Aβ. Other Aβ isoforms, such as truncated Aβ, have also been implicated in disease. However, developing a clear understanding of AD pathogenesis has been hampered by the complexity of Aβ biochemistry in vitro and in vivo. This review explores factors contributing to the lack of consistency in experimental approaches taken to model Aβ aggregation and toxicity and provides an overview of the different techniques available to analyse Aβ, such as electron and atomic force microscopy, nuclear magnetic resonance spectroscopy, dye-based assays, size exclusion chromatography, mass spectrometry and SDS-PAGE. The review also explores how different types of Aβ can influence Aβ aggregation and toxicity, leading to variation in experimental outcomes, further highlighting the need for standardisation in Aβ preparations and methods used in current research.
虽然存在争议，但淀粉样蛋白级联假说仍是阿尔茨海默病（AD）领域的核心理论，并假设β淀粉样蛋白（Aβ）是引发疾病发作的核心因素。近年来，人们越来越重视研究低分子量聚集体（如寡聚物）的作用，这些聚集体被认为比纤维状 Aβ更具神经毒性。其他 Aβ 亚型，如截断的 Aβ，也与疾病有关。然而，由于 Aβ 生化在体外和体内的复杂性，对 AD 发病机制的清晰理解一直受到阻碍。这篇综述探讨了导致 Aβ 聚集和毒性实验方法缺乏一致性的因素，并概述了可用于分析 Aβ 的不同技术，如电子和原子力显微镜、核磁共振波谱、染料基测定法、排阻色谱、质谱和 SDS-PAGE。该综述还探讨了不同类型的 Aβ 如何影响 Aβ 的聚集和毒性，导致实验结果的差异，进一步强调了在当前研究中需要对 Aβ 制剂和方法进行标准化。
