Bioengineering Laboratory, RIKEN Institute, Wako, Saitama, Japan.
FEBS J. 2010 Mar;277(6):1348-58. doi: 10.1111/j.1742-4658.2010.07568.x. Epub 2010 Feb 9.
Alzheimer's disease (AD) is an age-related, progressive degenerative disorder that is characterized by synapse and neuron loss in the brain and the accumulation of protein-containing deposits (referred to as 'senile plaques') and neurofibrillary tangles. Insoluble amyloid beta-peptide (Abeta) fibrillar aggregates found in extracellular plaques have long been thought to cause the neurodegenerative cascades of AD. However, accumulating evidence suggests that prefibrillar soluble Abeta oligomers induce AD-related synaptic dysfunction. The size of Abeta oligomers is distributed over a wide molecular weight range (from < 10 kDa to > 100 kDa), with structural polymorphism in Abeta oligomers of similar sizes. Recent studies have demonstrated that Abeta can accumulate in living cells, as well as in extracellular spaces. This review summarizes current research on Abeta oligomers, focusing on their structures and toxicity mechanism. We also discuss possible formation mechanisms of intracellular and extracellular Abeta oligomers.
阿尔茨海默病（AD）是一种与年龄相关的进行性神经退行性疾病，其特征是大脑中突触和神经元的丧失以及含有蛋白质的沉积物（称为“老年斑”）和神经原纤维缠结的积累。长期以来，人们一直认为存在于细胞外斑块中的不溶性淀粉样β肽（Abeta）纤维状聚集物会引发 AD 的神经退行性级联反应。然而，越来越多的证据表明，原纤维状可溶性 Abeta 寡聚体诱导 AD 相关的突触功能障碍。Abeta 寡聚体的大小分布在很宽的分子量范围内（<10 kDa 至>100 kDa），具有相似大小的 Abeta 寡聚体的结构多态性。最近的研究表明，Abeta 可以在活细胞以及细胞外空间中积累。本综述总结了 Abeta 寡聚体的当前研究，重点介绍了它们的结构和毒性机制。我们还讨论了细胞内和细胞外 Abeta 寡聚体的可能形成机制。
