Institute of Medical Biochemistry, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil.
Neurobiol Learn Mem. 2011 Nov;96(4):529-43. doi: 10.1016/j.nlm.2011.08.003. Epub 2011 Sep 6.
Alzheimer's disease (AD) is the 3rd most costly disease and the leading cause of dementia. It can linger for many years, but ultimately is fatal, the 6th leading cause of death. Alzheimer's disease (AD) is fatal and affected individuals can sometimes linger many years. Current treatments are palliative and transient, not disease modifying. This article reviews progress in the search to identify the primary AD-causing toxins. We summarize the shift from an initial focus on amyloid plaques to the contemporary concept that AD memory failure is caused by small soluble oligomers of the Aβ peptide, toxins that target and disrupt particular synapses. Evidence is presented that links Aβ oligomers to pathogenesis in animal models and humans, with reference to seminal discoveries from cell biology and new ideas concerning pathogenic mechanisms, including relationships to diabetes and Fragile X. These findings have established the oligomer hypothesis as a new molecular basis for the cause, diagnosis, and treatment of AD.
阿尔茨海默病（AD）是第三大昂贵的疾病，也是痴呆症的主要原因。它可以持续多年，但最终是致命的，是第六大死亡原因。阿尔茨海默病（AD）是致命的，受影响的个体有时会持续多年。目前的治疗方法是姑息性和短暂性的，不能改变疾病。本文综述了寻找导致 AD 的主要毒素的进展。我们总结了从最初关注淀粉样斑块到当前概念的转变，即 AD 记忆失败是由 Aβ肽的小可溶性寡聚物引起的，这些毒素针对并破坏特定的突触。有证据表明，Aβ寡聚物与动物模型和人类的发病机制有关，并参考了细胞生物学的开创性发现和有关发病机制的新想法，包括与糖尿病和脆性 X 综合征的关系。这些发现将寡聚体假说确立为 AD 病因、诊断和治疗的新分子基础。
