Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40225, Düsseldorf, Germany.
Institute of Complex Systems, Structural Biochemistry (ICS-6), Forschungszentrum Jülich, 52425, Jülich, Germany.
Sci Rep. 2017 May 30;7(1):2493. doi: 10.1038/s41598-017-02370-3.
Amyloid β (Aβ) oligomers may play a decisive role in Alzheimer's disease related neurodegeneration, but their structural properties are poorly understood. In this report, sedimentation velocity centrifugation, small angle neutron scattering (SANS) and molecular modelling were used to identify the small oligomeric species formed by the 42 amino acid residue long isoform of Aβ (Aβ42) in solution, characterized by a sedimentation coefficient of 2.56 S, and a radius of gyration between 2 and 4 nm. The measured sedimentation coefficient is in close agreement with the sedimentation coefficient calculated for Aβ42 hexamers using MD simulations at µM concentration. To the best of our knowledge this is the first report detailing the Aβ42 oligomeric species by SANS measurements. Our results demonstrate that the smallest detectable species in solution are penta- to hexamers. No evidences for the presence of dimers, trimers or tetramers were found, although the existence of those Aβ42 oligomers at measurable quantities had been reported frequently.
淀粉样蛋白 β (Aβ) 寡聚体可能在阿尔茨海默病相关的神经退行性变中起决定性作用，但它们的结构特性仍知之甚少。在本报告中，沉降速度离心、小角中子散射 (SANS) 和分子建模被用于鉴定在溶液中形成的 42 个氨基酸残基长的 Aβ (Aβ42) 的小寡聚体物种，其特征在于沉降系数为 2.56 S，并且回转半径在 2 到 4nm 之间。测量的沉降系数与使用 MD 模拟在 µM 浓度下计算的 Aβ42 六聚体的沉降系数非常吻合。据我们所知，这是首次通过 SANS 测量详细描述 Aβ42 寡聚体的报告。我们的结果表明，溶液中最小可检测的物种是五聚体到六聚体。虽然经常有报道称存在可测量量的那些 Aβ42 寡聚体，但没有发现二聚体、三聚体或四聚体的存在证据。
