The structural polymorphism and the physiological and pathophysiological roles of two important proteins, β-amyloid (Aβ) and tau, that play a key role in Alzheimer’s disease (AD) are reviewed. Recent results demonstrate that monomeric Aβ has important physiological functions. Toxic oligomeric Aβ assemblies (AβOs) may play a decisive role in AD pathogenesis. The polymorph fibrillar Aβ (fAβ) form has a very ordered cross-β structure and is assumed to be non-toxic. Tau monomers also have several important physiological actions; however, their oligomerization leads to toxic oligomers (TauOs). Further polymerization results in probably non-toxic fibrillar structures, among others neurofibrillary tangles (NFTs). Their structure was determined by cryo-electron microscopy at atomic level. Both AβOs and TauOs may initiate neurodegenerative processes, and their interactions and crosstalk determine the pathophysiological changes in AD. TauOs (perhaps also AβO) have prionoid character, and they may be responsible for cell-to-cell spreading of the disease. Both extra- and intracellular AβOs and TauOs (and not the previously hypothesized amyloid plaques and NFTs) may represent the novel targets of AD drug research.

中文翻译：

---

寡聚化和构象变化使单体 β-淀粉样蛋白和 Tau 蛋白有毒：它们在阿尔茨海默病发病机制中的作用

综述了在阿尔茨海默病 (AD) 中起关键作用的两种重要蛋白质 β-淀粉样蛋白 (Aβ) 和 tau 的结构多态性以及生理和病理生理学作用。最近的结果表明单体 Aβ 具有重要的生理功能。有毒的寡聚 Aβ 组装体 (AβOs) 可能在 AD 发病机制中起决定性作用。多晶型纤维状 Aβ (fAβ) 形式具有非常有序的交叉 β 结构，并且被认为是无毒的。Tau 单体还具有几个重要的生理作用；然而，它们的低聚会导致有毒的低聚物 (TauOs)。进一步聚合可能会产生无毒的纤维状结构，其中包括神经纤维缠结 (NFT)。它们的结构是通过原子水平的低温电子显微镜确定的。AβOs 和 TauOs 都可能引发神经退行性过程，它们的相互作用和串扰决定了 AD 的病理生理变化。TauOs（也许还有 AβO）具有朊病毒特征，它们可能是疾病细胞间传播的原因。细胞外和细胞内的 AβOs 和 TauOs（而不是之前假设的淀粉样蛋白斑块和 NFTs）可能代表 AD 药物研究的新目标。