Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, 39011 Santander, Spain.
Int J Mol Sci. 2020 Sep 20;21(18):6906. doi: 10.3390/ijms21186906.
Down syndrome (DS), the most common cause of intellectual disability of genetic origin, is characterized by alterations in central nervous system morphology and function that appear from early prenatal stages. However, by the fourth decade of life, all individuals with DS develop neuropathology identical to that found in sporadic Alzheimer's disease (AD), including the development of amyloid plaques and neurofibrillary tangles due to hyperphosphorylation of tau protein, loss of neurons and synapses, reduced neurogenesis, enhanced oxidative stress, and mitochondrial dysfunction and neuroinflammation. It has been proposed that DS could be a useful model for studying the etiopathology of AD and to search for therapeutic targets. There is increasing evidence that the neuropathological events associated with AD are interrelated and that many of them not only are implicated in the onset of this pathology but are also a consequence of other alterations. Thus, a feedback mechanism exists between them. In this review, we summarize the signalling pathways implicated in each of the main neuropathological aspects of AD in individuals with and without DS as well as the interrelation of these pathways.
唐氏综合征（Down syndrome，DS）是最常见的遗传性智力障碍病因，其特征为中枢神经系统形态和功能发生改变，这些改变从早期产前阶段就开始出现。然而，到了人生的第四个十年，所有患有 DS 的人都会出现与散发性阿尔茨海默病（Alzheimer's disease，AD）相同的神经病理学表现，包括由于 tau 蛋白过度磷酸化而导致的淀粉样斑块和神经原纤维缠结的形成、神经元和突触的丧失、神经发生减少、氧化应激增强以及线粒体功能障碍和神经炎症。有人提出，DS 可能是研究 AD 病因病理学和寻找治疗靶点的有用模型。越来越多的证据表明，与 AD 相关的神经病理学事件是相互关联的，其中许多不仅与该病理学的发生有关，而且也是其他改变的后果。因此，它们之间存在反馈机制。在这篇综述中，我们总结了在患有和不患有 DS 的个体的 AD 的主要神经病理学方面涉及的信号通路，以及这些通路之间的相互关系。
