Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by pathological aggregates of amyloid β-protein (Aβ) and tau protein. On the basis of genetic evidence, biochemical data, and animal models, Aβ has been suggested to be responsible for the pathogenesis of AD (the amyloid hypothesis). Aβ molecules tend to aggregate to form oligomers, protofibrils, and mature fibrils. Although mature fibrils in the final stage have been thought to be the cause of AD pathogenesis, recent studies using synthetic Aβ peptides, a cell culture model, Aβ precursor protein transgenic mice models, and human samples, such as cerebrospinal fluids and postmortem brains of AD patients, suggest that pre-fibrillar forms (oligomers of Aβ) are more deleterious than are extracellular fibril forms. Based on this recent evidence showing that oligomers have a central role in the pathogenesis of AD, the term “oligomeropathy” could be used to define AD and other protein-misfolding diseases.

In this review, I discuss recent developments in the “oligomer hypothesis” including our research findings regarding the pathogenesis of AD.

阿尔茨海默氏病（AD）是最常见的年龄相关性神经退行性疾病，其特征在于淀粉样蛋白β-蛋白（Aβ）和tau蛋白的病理性聚集。根据遗传证据，生化数据和动物模型，已建议Aβ负责AD的发病机理（淀粉样假说）。Aβ分子倾向于聚集形成低聚物，原纤维和成熟纤维。尽管最后阶段的成熟原纤维被认为是AD发病的原因，但最近的研究使用合成的Aβ肽，细胞培养模型，Aβ前体蛋白转基因小鼠模型和人类样品，例如AD的脑脊髓液和死后大脑这些患者认为，原纤维形式（Aβ的寡聚体）比细胞外原纤维形式更有害。

在这篇综述中，我讨论了“低聚物假说”的最新发展，包括我们关于AD发病机理的研究发现。