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阿尔茨海默病的小鼠模型。

Mouse models of Alzheimer's disease.

机构信息

Center for Neurodegeneration and Experimental Therapeutics, Departments of Neurology and Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

出版信息

Brain Res Bull. 2012 May 1;88(1):3-12. doi: 10.1016/j.brainresbull.2011.11.017. Epub 2011 Nov 28.

DOI:10.1016/j.brainresbull.2011.11.017
PMID:22142973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3546481/
Abstract

Alzheimer's disease (AD) is the most common cause of dementia, affecting 35 million people today. The search for new treatments is made ever more urgent by prospects for increasing prevalence due to population aging. Mouse models are one of the most important research tools for finding new treatments for AD. Here, we review those models. We begin by briefly reviewing the AD genetics on which mouse models are based and then consider the most common mouse models of AD, including mice transgenic for human amyloid precursor protein (hAPP) and beta-amyloid (Aβ), mice expressing mutant presenilin genes, mice modeling tau's role in AD, and apolipoprotein E models. The discussion highlights key features and important differences between these mouse models. We conclude with a discussion about the role of AD mouse models in the translational pipeline.

摘要

阿尔茨海默病(AD)是痴呆症最常见的病因,目前影响着 3500 万人。由于人口老龄化,预计 AD 的患病率将会增加,因此对新疗法的探索变得更加紧迫。小鼠模型是寻找 AD 新疗法的最重要的研究工具之一。在这里,我们将对这些模型进行综述。我们首先简要回顾一下 AD 的遗传基础,然后考虑 AD 的最常见的小鼠模型,包括表达人淀粉样前体蛋白(hAPP)和β-淀粉样蛋白(Aβ)的转基因小鼠、表达突变早老素基因的小鼠、模拟 AD 中 tau 作用的小鼠以及载脂蛋白 E 模型。讨论强调了这些小鼠模型之间的关键特征和重要差异。最后,我们讨论了 AD 小鼠模型在转化研究中的作用。

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本文引用的文献

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J Neurosci. 2011 May 25;31(21):7691-9. doi: 10.1523/JNEUROSCI.6637-10.2011.
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The many faces of tau.tau 的多面性。
Neuron. 2011 May 12;70(3):410-26. doi: 10.1016/j.neuron.2011.04.009.
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The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.
超越转基因小鼠:阿尔茨海默病的新兴模型与转化策略
Int J Mol Sci. 2025 Jun 10;26(12):5541. doi: 10.3390/ijms26125541.
4
Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.阿尔茨海默病建模:基因修饰和诱导动物模型、复杂细胞培养模型及计算建模综述
Brain Sci. 2025 May 5;15(5):486. doi: 10.3390/brainsci15050486.
5
Shared early molecular mechanisms revealed in P301S and 5xFAD Alzheimer's disease mouse models.在P301S和5xFAD阿尔茨海默病小鼠模型中揭示的共同早期分子机制。
Transl Psychiatry. 2025 Mar 26;15(1):97. doi: 10.1038/s41398-025-03321-7.
6
Pharmacological inhibition of PLK2 kinase activity mitigates cognitive decline but aggravates APP pathology in a sex-dependent manner in APP/PS1 mouse model of Alzheimer's disease.在阿尔茨海默病的APP/PS1小鼠模型中,PLK2激酶活性的药理学抑制可减轻认知衰退,但会以性别依赖性方式加重APP病理学改变。
Heliyon. 2024 Oct 18;10(20):e39571. doi: 10.1016/j.heliyon.2024.e39571. eCollection 2024 Oct 30.
7
The IGF System and Aging.胰岛素样生长因子系统与衰老
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Alzheimers Dement. 2011 May;7(3):263-9. doi: 10.1016/j.jalz.2011.03.005. Epub 2011 Apr 21.
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The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.阿尔茨海默病所致轻度认知障碍的诊断:美国国家老龄化研究所-阿尔茨海默病协会诊断指南工作组的建议。
Alzheimers Dement. 2011 May;7(3):270-9. doi: 10.1016/j.jalz.2011.03.008. Epub 2011 Apr 21.
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Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease.为了定义阿尔茨海默病的临床前阶段:来自美国国家老龄化研究所-阿尔茨海默病协会工作组关于阿尔茨海默病诊断指南的建议。
Alzheimers Dement. 2011 May;7(3):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21.
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Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.MS4A4/MS4A6E、CD2AP、CD33 和 EPHA1 上的常见变异与晚发性阿尔茨海默病相关。
Nat Genet. 2011 May;43(5):436-41. doi: 10.1038/ng.801. Epub 2011 Apr 3.
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Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.载脂蛋白 A7(ABCA7)、膜表面抗原 4A6A/4A4E(MS4A6A/MS4A4E)、EPH 受体 A1(EPHA1)、CD33 和 CD2 相关蛋白激酶 A(CD2AP)上的常见变异与阿尔茨海默病有关。
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Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease.淀粉样蛋白-β/Fyn 诱导的突触、网络和认知障碍依赖于阿尔茨海默病多种小鼠模型中的 tau 水平。
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Amyloid-β and tau--a toxic pas de deux in Alzheimer's disease.β淀粉样蛋白和 tau--阿尔茨海默病中的毒性双人舞。
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