Transgenic models of Alzheimer's disease: better utilization of existing models through viral transgenesis.

Transgenic models of Alzheimer's disease: better utilization of existing models through viral transgenesis.
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DOI:
10.1016/j.bbadis.2013.04.017
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发表时间:
2013-09
影响因子:
6.2
通讯作者:
Murphy, M. Paul
Murphy, M. Paul
中科院分区:
生物学2区
文献类型:
--
作者:
Platt, Thomas L.;Reeves, Valerie L.;Murphy, M. Paul

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动物模型已经在阿尔茨海默病(AD)研究领域使用了几十年,并且对于我们对该疾病的理解的进步至关重要。大多数模型基于参与淀粉样蛋白形成过程的基因的家族性AD突变,例如淀粉样蛋白前体蛋白(APP)和早老素1(PS1)。一些模型还包含已知引起额颞叶痴呆的tau(MAPT)突变,这是一种神经退行性疾病,与AD共享一些神经病理学要素。虽然这些模型很复杂,但它们未能显示出完美再现人类疾病的病理学。不幸的是,这种预先存在的复杂程度对这些模型的进一步修改和改进造成了障碍。然而,随着病毒载体的有效性和安全性的提高,它们作为种系遗传修饰的替代品正在成为一种广泛使用的研究工具。在这篇综述中,我们将讨论如何使用这种方法来更好地利用常见的小鼠模型在AD研究。
Animal models have been used for decades in the Alzheimer’s disease (AD) research field and have been crucial for the advancement of our understanding of the disease. Most models are based on familial AD mutations of genes involved in the amyloidogenic process, such as the amyloid precursor protein (APP) and presenilin 1 (PS1). Some models also incorporate mutations in tau (MAPT) known to cause frontotemporal dementia, a neurodegenerative disease that shares some elements of neuropathology with AD. While these models are complex, they fail to display pathology that perfectly recapitulates that of the human disease. Unfortunately, this level of pre-existing complexity creates a barrier to the further modification and improvement of these models. However, as the efficacy and safety of viral vectors improves, their use as an alternative to germline genetic modification is becoming a widely used research tool. In this review we discuss how this approach can be used to better utilize common mouse models in AD research.
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