Mc Donald Jessica M, O'Malley Tiernan T, Liu Wen, Mably Alexandra J, Brinkmalm Gunnar, Portelius Erik, Wittbold William M, Frosch Matthew P, Walsh Dominic M
Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA.
Laboratory for Neurodegenerative Research, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA; School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Republic of Ireland.
Alzheimers Dement. 2015 Nov;11(11):1286-305. doi: 10.1016/j.jalz.2015.01.005. Epub 2015 Apr 4.
Much knowledge about amyloid β (Aβ) aggregation and toxicity has been acquired using synthetic peptides and mouse models, whereas less is known about soluble Aβ in human brain.
We analyzed aqueous extracts from multiple AD brains using an array of techniques.
Brains can contain at least four different Aβ assembly forms including: (i) monomers, (ii) a ∼7 kDa Aβ species, and larger species (iii) from ∼30-150 kDa, and (iv) >160 kDa. High molecular weight species are by far the most prevalent and appear to be built from ∼7 kDa Aβ species. The ∼7 kDa Aβ species resist denaturation by chaotropic agents and have a higher Aβ42/Aβ40 ratio than monomers, and are unreactive with antibodies to Asp1 of Ab or APP residues N-terminal of Asp1.
Further analysis of brain-derived ∼7 kDa Aβ species, the mechanism by which they assemble and the structures they form should reveal therapeutic and diagnostic opportunities.
利用合成肽和小鼠模型已经获得了许多关于淀粉样β蛋白（Aβ）聚集和毒性的知识，而对于人脑中可溶性Aβ的了解较少。
我们使用一系列技术分析了多个阿尔茨海默病（AD）大脑的水提取物。
大脑中至少可含有四种不同的Aβ组装形式，包括：（i）单体，（ii）一种约7 kDa的Aβ种类，以及更大的种类（iii）约30 - 150 kDa，和（iv）>160 kDa。迄今为止，高分子量种类最为普遍，且似乎由约7 kDa的Aβ种类构成。约7 kDa的Aβ种类能抵抗离液剂的变性作用，且Aβ42/Aβ40比值高于单体，并且与针对Aβ的Asp1或Asp1 N端APP残基的抗体无反应。
对源自大脑的约7 kDa Aβ种类、它们的组装机制以及所形成结构的进一步分析应能揭示治疗和诊断机会。
