Recent investigations suggest that soluble oligomeric amyloid β (Aβ) species may be involved in early onset of Alzheimer's disease (AD). Using systematic proline replacement, solid-state NMR, and ESR, we identified a toxic turn at position 22 and 23 of Aβ42, the most potent neurotoxic Aβ species. Through radicalization, the toxic turn can induce formation of the C-terminal hydrophobic core to obtain putative Aβ42 dimers and trimers. Synthesized dimer and trimer models showed that the C-terminal hydrophobic core plays a critical role in the formation of high molecular weight oligomers with neurotoxicity. Accordingly, an anti-toxic turn antibody (24B3) that selectively recognizes a toxic dimer model of E22P-Aβ42 was developed. Sandwich enzyme-linked immunosorbent assay with 24B3 and 82E1 detected a significantly higher ratio of Aβ42 with a toxic turn to total Aβ42 in cerebrospinal fluid of AD patients compared with controls, suggesting that 24B3 could be useful for early onset of AD diagnosis.

中文翻译：

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基于淀粉样蛋白β的毒性构象理论的阿尔茨海默氏病诊断新方法。

最近的研究表明，可溶性寡聚淀粉样β（Aβ）物种可能与阿尔茨海默氏病（AD）的早期发作有关。使用系统的脯氨酸替代，固态NMR和ESR，我们在Aβ42（最有力的神经毒性Aβ物种）的22和23位确定了毒性转折。通过自由基作用，毒性转向可以诱导C端疏水核的形成，从而获得推定的Aβ42二聚体和三聚体。合成的二聚体和三聚体模型表明，C端疏水核在具有神经毒性的高分子量低聚物形成中起关键作用。因此，开发了选择性识别E22P-Aβ42的毒性二聚体模型的抗毒性转向抗体（24B3）。