Development and characterization of an aged onset model of Alzheimer's disease in Drosophila melanogaster
Development and characterization of an aged onset model of Alzheimer's disease in Drosophila melanogaster
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DOI：
10.1016/j.expneurol.2014.08.021
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发表时间：
2014-11-01
影响因子：
5.3
通讯作者：
Marenda, Daniel R.
中科院分区：
文献类型：
--
作者：
Mhatre, Siddhita D.;Michelson, Sarah J.;Marenda, Daniel R.
老年痴呆症（AD）的最大危险因素是年龄。取决于发病年龄。AD在临床上分为早发型（60岁之前）或晚发型（65岁之后），绝大多数AD被诊断为晚发型（LOAD）。LOAD是一种进行性神经退行性疾病，涉及老年患者大脑中β-淀粉样蛋白（A β）斑块和神经元缠结的积累。受影响的人经常会出现症状，包括记忆丧失，混乱和行为改变。尽管存在许多AD动物模型，但很少有人能够分析老年对AD病理学的影响。为了更好地模拟LOAD，我们使用果蝇开发了一种新的“老年AD”模型。在我们的模型中，我们表达低水平的人类AD蛋白APP（淀粉样前体蛋白）和BACE 1（β位点APP裂解酶BACE），特别是在苍蝇的中枢神经系统中。我们的模型的优点包括在果蝇的寿命后期由于中枢神经系统（CNS）内A β的逐渐累积而出现行为和神经病理学症状，使年龄成为我们在该模型中观察到的行为和神经解剖学表型的关键因素。(C)2014 Elsevier Inc. All rights reserved.
The biggest risk factor for developing Alzheimer's disease (AD) is age. Depending on the age of onset. AD is clinically categorized into either the early-onset form (before age 60 years old), or the late-onset form (after age 65 years old), with the vast majority of AD diagnosed as late onset (LOAD). LOAD is a progressive neurodegenerative disorder that involves the accumulation of beta-amyloid (A beta) plaques and neurofibrillary tangles in the brains of elderly patients. Affected individuals often experience symptoms including memory loss, confusion, and behavioral changes. Though many animal models of AD exist, very few are capable of analyzing the effect of older age on AD pathology. In an attempt to better model LOAD, we developed a novel "aged AD" model using Drosophila melanogaster. In our model, we express low levels of the human AD proteins APP (amyloid precursor protein) and BACE1 (beta-site APP cleaving enzyme BACE) specifically in the fly's central nervous system. Advantages of our model include the onset of behavioral and neuropathological symptoms later in the fly's lifespan due to a gradual accrual of A beta within the central nervous system (CNS), making age the key factor in the behavioral and neuroanatomical phenotypes that we observe in this model. (C) 2014 Elsevier Inc. All rights reserved.