University of Zurich, Switzerland.
J Alzheimers Dis. 2010;22 Suppl 3:5-19. doi: 10.3233/JAD-2010-100975.
Alzheimer's disease (AD) is the most common form of dementia, which affects more than 35 million people worldwide with increasing tendency. Satisfying therapies and prevention are not available. Since the first description of the fatal progressive neurodegenerative disease in 1907, however, major findings on the molecular mechanisms have been reported. Current clinical trials target diverse aspects and principles of AD, such as the generation and aggregation of amyloid-β (Aβ). Extracellular amyloid plaques, predominantly consisting of Aβ, and intracellular neurofibrillar tangles, formed by hyperphosphorylated tau, are the major pathological hallmarks in the brain of AD patients. AD is consequently one of about 40 identified amyloidoses - protein misfolding diseases, which share as their main pathogenic mechanism the aberrant deposition of endogenous proteins as amyloid fibrils. This article aims principally to introduce AD and its identified key players, to summarize classic and recent publications on the complex molecular mechanisms underlying the disease, and to discuss challenges that need to be faced for the development of improved therapeutic strategies.
阿尔茨海默病（AD）是最常见的痴呆症形式，全球有超过 3500 万人受到影响，且呈上升趋势。目前尚无令人满意的治疗和预防方法。自 1907 年首次描述这种致命的进行性神经退行性疾病以来，已经有关于其分子机制的主要发现。目前的临床试验针对 AD 的多个方面和原则，例如淀粉样蛋白-β（Aβ）的产生和聚集。细胞外淀粉样斑块，主要由 Aβ组成，以及由过度磷酸化的 tau 形成的细胞内神经原纤维缠结，是 AD 患者大脑中的主要病理标志物。AD 是大约 40 种已识别的淀粉样变性病之一 - 蛋白质错误折叠疾病，其主要致病机制是内源性蛋白质异常沉积为淀粉样纤维。本文主要旨在介绍 AD 及其已确定的关键参与者，总结疾病背后复杂的分子机制的经典和最新文献，并讨论为开发改进的治疗策略而需要面对的挑战。
