Amyloid-beta (Abeta) oligomers consist of fibrillar and non-fibrillar soluble assemblies of the Abeta peptide. Tg2576 human amyloid precursor protein (APP)-expressing transgenic mice modeling Alzheimer disease produce Abeta*56, a non-fibrillar Abeta assembly that has been shown by several groups to relate more closely to memory deficits than plaques. Previous studies did not decipher specific forms of Abeta present in Abeta*56. Here, we confirm and extend the biochemical characterization of Abeta*56. We used anti-Abeta(1-x), anti-Abeta(x-40), and A11 anti-oligomer antibodies in conjunction with western blotting, immunoaffinity purification, and size-exclusion chromatography to probe aqueous brain extracts from Tg2576 mice of different ages. We found that Abeta*56 is a ~56-kDa, SDS-stable, A11-reactive, non-plaque-related, water-soluble, brain-derived oligomer containing canonical Abeta(1-40) that correlates with age-related memory loss. The unusual stability of this high molecular-weight oligomer renders it an attractive candidate for studying relationships between molecular structure and effects on brain function.

中文翻译：

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Abeta * 56 是一种稳定的低聚物，与 Tg2576 小鼠的年龄相关记忆丧失相关

淀粉样蛋白-β (Abeta) 低聚物由 Abeta 肽的纤维状和非纤维状可溶性组件组成。表达 Tg2576 人淀粉样蛋白前体蛋白 (APP) 的转基因小鼠模拟阿尔茨海默病产生 Abeta * 56，这是一种非纤维状 Abeta 组件，已被几个小组证明与记忆缺陷的关系比斑块更密切。以前的研究没有破译 Abeta * 56 中存在的特定形式的 Abeta。在这里，我们确认并扩展了 Abeta * 56 的生化特征。我们使用抗 Abeta (1-x)、抗 Abeta (x-40) 和 A11 抗寡聚体抗体，结合蛋白质印迹、免疫亲和纯化和体积排阻层析来探测来自不同 Tg2576 小鼠的脑水提取物年龄。我们发现 Abeta*56 是一种 ~56-kDa、SDS 稳定、A11 反应、非斑块相关、水溶性、含有与年龄相关的记忆丧失相关的典型 Abeta(1-40) 的脑源性低聚物。这种高分子量低聚物的不寻常稳定性使其成为研究分子结构与对脑功能影响之间关系的有吸引力的候选者。