Centre de Regulació Genòmica, UPF, Parc de Recerca Biomèdica de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras, Spain.
CNS Neurol Disord Drug Targets. 2010 Aug;9(4):429-38. doi: 10.2174/187152710791556159.
Individuals with trisomy 21, also known as Down syndrome (DS), develop a clinical syndrome including almost identical neuropathological characteristics of Alzheimer's disease (AD) observed in non-DS individuals. The main difference is the early age of onset of AD pathology in individuals with DS, with hish incidence of clinical symptoms in the late 40- early 50 years of age. The neuropathology of AD in persons with DS is superimposed with the developmental abnormalities causing alterations of neuronal morphology and function. Despite the ubiquitous occurrence of AD neuropathology, clinical signs of dementia do not occur in all adults with DS even at older ages. Phenotype analysis of DS mouse models has revealed a differential age-related neurodegenerative pattern that correlates with specific biochemical and molecular alterations at the cellular level. In fact, several individual genes found in trisomy in DS have been functionally related to neuronal degeneration. Thus, mouse models overexpressing HSA21 gene(s) are fundamental to understand the neurodegenerative process in DS, as described in the present review. In addition, these models might allow to define and evaluate potential drug targets and to develop therapeutic strategies that may interfere or delay the onset of AD.
个体患有 21 三体综合征，也称为唐氏综合征（DS），会发展出一种临床综合征，包括与非 DS 个体中观察到的阿尔茨海默病（AD）几乎完全相同的神经病理学特征。主要区别在于 DS 个体中 AD 病理学的发病年龄更早，在 40 岁后期至 50 岁早期出现高发生率的临床症状。AD 在 DS 个体中的神经病理学与导致神经元形态和功能改变的发育异常叠加在一起。尽管 AD 神经病理学普遍存在，但并非所有 DS 成年人甚至在老年时都会出现痴呆的临床症状。DS 小鼠模型的表型分析揭示了一种与特定细胞水平的生化和分子改变相关的、具有差异的年龄相关神经退行性模式。事实上，在 DS 三体中发现的几个个体基因与神经元变性具有功能相关性。因此，正如本综述所述，过表达 HSA21 基因的小鼠模型对于理解 DS 中的神经退行性过程至关重要。此外，这些模型可能有助于确定和评估潜在的药物靶点，并开发可能干扰或延迟 AD 发病的治疗策略。
