Sasahara Kenji, Morigaki Kenichi, Mori Yasuko
Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
Research Center for Environmental Genomics, Kobe University, Kobe 657-8501, Japan.
Anal Biochem. 2015 Jul 15;481:18-26. doi: 10.1016/j.ab.2015.04.014. Epub 2015 Apr 20.
Amyloid aggregation and deposition of amyloid β-peptide (Aβ) are pathologic characteristics of Alzheimer's disease (AD). Recent reports have shown that the association of Aβ with membranes containing ganglioside GM1 (GM1) plays a pivotal role in amyloid deposition and the pathogenesis of AD. However, the molecular interactions responsible for membrane damage associated with Aβ deposition are not fully understood. In this study, we microscopically observed amyloid aggregation of Aβ in the presence of lipid vesicles and on a substrate-supported planar membrane containing raft components and GM1. The experimental system enabled us to observe lipid-associated aggregation of Aβ, uptake of the raft components into Aβ aggregates, and relevant membrane damage. The results indicate that uptake of raft components from the membrane into Aβ deposits induces macroscopic heterogeneity of the membrane structure.
淀粉样蛋白聚集以及淀粉样β肽（Aβ）沉积是阿尔茨海默病（AD）的病理特征。最近的报道表明，Aβ与含有神经节苷脂GM1（GM1）的膜之间的关联在淀粉样蛋白沉积和AD发病机制中起关键作用。然而，与Aβ沉积相关的膜损伤所涉及的分子相互作用尚未完全明确。在本研究中，我们通过显微镜观察了在脂质囊泡存在的情况下以及在含有筏组分和GM1的底物支撑平面膜上Aβ的淀粉样蛋白聚集情况。该实验系统使我们能够观察到与脂质相关的Aβ聚集、筏组分被摄取到Aβ聚集体中以及相关的膜损伤。结果表明，筏组分从膜中被摄取到Aβ沉积物中会导致膜结构的宏观异质性。
