Sturchler-Pierrat C, Sommer B
Novartis Pharma Inc., Nervous System Research, Basel, Switzerland.
Rev Neurosci. 1999;10(1):15-24. doi: 10.1515/revneuro.1999.10.1.15.
Alzheimer's disease (AD) is a neurodegenerative disorder of the brain accounting for about 50-70% of the typical late onset cases of dementia. The pathological and diagnostic hallmarks of the disease are principally the presence of extracellular deposits called neuritic amyloid plaques and the intracellular aggregation of neurofibrillary tangles. In addition selective neuronal cell loss accompanied by cerebrovascular amyloidosis is detectable. In the case of familial AD, defects in at least three different genes (APP, PS1, PS2) leading to indistinguishable pathology are now well defined. There is as yet no real treatment for AD. Therefore the availability of an easily manipulable animal model is crucial for the development of new drugs, which could slow down or, even better, stop the progression of the disease. The development and originality of such experimental models that could greatly facilitate the investigation of the aetiology and pathogenesis of AD are described and discussed in this review. They are based mainly on the attempt to reproduce the neurofibrillary tangles or the amyloid deposits and plaque formation.
阿尔茨海默病（AD）是一种脑部神经退行性疾病，约占典型晚发型痴呆病例的50 - 70%。该疾病的病理和诊断标志主要是存在称为神经炎性淀粉样斑块的细胞外沉积物以及神经原纤维缠结的细胞内聚集。此外，还可检测到伴有脑血管淀粉样变性的选择性神经元细胞丢失。在家族性AD病例中，导致难以区分的病理变化的至少三种不同基因（APP、PS1、PS2）的缺陷现已明确。目前尚无针对AD的有效治疗方法。因此，拥有一种易于操作的动物模型对于开发能够减缓甚至更好地阻止疾病进展的新药至关重要。本文综述描述并讨论了此类能够极大促进AD病因学和发病机制研究的实验模型的开发和创新性。它们主要基于重现神经原纤维缠结或淀粉样沉积物及斑块形成的尝试。
