Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice:: A role for intraneuronal amyloid
Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice:: A role for intraneuronal amyloid
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DOI：
10.1016/j.neubiorev.2006.07.007
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发表时间：
2007-01-01
影响因子：
8.2
通讯作者：
Fernandez-Teruel, A.
中科院分区：
文献类型：
--
作者：
Gimenez-Llort, L.;Blazquez, G.;Fernandez-Teruel, A.
淀粉样蛋白A β-肽（A β）被怀疑在导致AD的级联反应中起关键作用，AD是导致神经元和突触功能障碍并最终导致细胞死亡的病原体。因此，它一直是关于这种疾病的大量临床和基础研究的主题。通常发现β聚集在细胞外淀粉样蛋白斑块中，所述斑块发生在阿尔茨海默病（AD）和唐氏综合征（DS）脑中富含nAChR的特定脑区域中。其熟悉和散发形式的遗传学进展，以及基因转移技术的进展，提供了有价值的动物模型，补充了传统的胆碱能方法，虽然在这些模型中模拟AD的神经元和行为缺陷一直具有挑战性。最近，新出现的证据表明A β的神经元内蓄积也可能导致神经退行性事件的级联反应，并强烈表明它是AD发作以及相关认知和其他行为缺陷的早期病理学生物标志物。本综述涵盖了这些研究在人类，在体外和转基因模型，也提供了更多的证据表明，成年3 x Tg-AD小鼠窝藏PSIM 146 V，APP（Swe），tau（P301 L）转基因，并模仿许多关键的标志性AD，显示认知缺陷和其他行为改变的年龄时，尚未观察到明显的神经病理学，但当神经元内A β，已经可以描述突触和胆碱能缺陷。(c)2006爱思唯尔有限公司保留所有权利。
The amyloid A beta-peptide (A beta) is suspected to play a critical role in the cascade leading to AD as the pathogen that causes neuronal and synaptic dysfunction and, eventually, cell death. Therefore, it has been the subject of a huge number of clinical and basic research studies on this disease. A beta is typically found aggregated in extracellular amyloid plaques that occur in specific brain regions enriched in nAChRs in Alzheimer's disease (AD) and Down syndrome (DS) brains. Advances in the genetics of its familiar and sporadic forms, together with those in gene transfer technology, have provided valuable animal models that complement the traditional cholinergic approaches, although modeling the neuronal and behavioral deficits of AD in these models has been challenging. More recently, emerging evidence indicates that intraneuronal accumulation of A beta may also contribute to the cascade of neurodegenerative events and strongly suggest that it is an early, pathological biomarker for the onset of AD and associated cognitive and other behavioral deficits. The present review covers these studies in humans, in in vitro and in transgenic models, also providing more evidence that adult 3 x Tg-AD mice harboring PSIM146V, APP(Swe), tau(P301L) transgenes, and mimicking many critical hallmarks of AD, show cognitive deficits and other behavioral alterations at ages when overt neuropathology is not yet observed, but when intraneuronal A beta, synaptic and cholinergic deficits can already be described. (c) 2006 Elsevier Ltd. All rights reserved.