Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of Alzheimer's Disease.
Systematic Phenotyping and Characterization of the 3xTg-AD Mouse Model of Alzheimer's Disease.
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DOI：
10.3389/fnins.2021.785276
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发表时间：
2021
影响因子：
4.3
通讯作者：
LaFerla FM
中科院分区：
文献类型：
--
作者：
Javonillo DI;Tran KM;Phan J;Hingco E;Kramár EA;da Cunha C;Forner S;Kawauchi S;Milinkeviciute G;Gomez-Arboledas A;Neumann J;Banh CE;Huynh M;Matheos DP;Rezaie N;Alcantara JA;Mortazavi A;Wood MA;Tenner AJ;MacGregor GR;Green KN;LaFerla FM
疾病的动物模型是研究致病机制和潜在治疗干预的宝贵资源。然而，对于复杂的疾病，如阿尔茨海默病（AD），无数不同的动物模型的产生和可用性提出了独特的挑战，AD研究人员和阻碍有用的治疗的成功。在这里，我们对AD的3xTg-AD小鼠模型在其整个生命周期进行了深入分析，以更好地了解在特定年龄出现的各种病理学领域，并评论自20年前发展以来在这一系列病理学发展中发生的漂移。3xTg-AD模型的现代表征包括评估长时程增强的损伤，然后定量β淀粉样蛋白（Aβ）斑块负荷和神经元tau缠结、Aβ和tau蛋白的生化水平以及神经病理学标志物，如神经胶质增生和营养不良性神经突的积累。我们还使用相同的深度表型表征管道对3xTg-AD模型与5xFAD模型进行了新的比较，并显示血浆NfL受斑块负荷的强烈驱动。这些分析的结果可通过AD知识门户网站（https：//modeladexplorer.org/）免费获得。我们的工作证明了表征管道的实用性，该管道生成与调查和比较当前和未来AD模型的疾病病因相关的稳健和标准化信息。
Animal models of disease are valuable resources for investigating pathogenic mechanisms and potential therapeutic interventions. However, for complex disorders such as Alzheimer’s disease (AD), the generation and availability of innumerous distinct animal models present unique challenges to AD researchers and hinder the success of useful therapies. Here, we conducted an in-depth analysis of the 3xTg-AD mouse model of AD across its lifespan to better inform the field of the various pathologies that appear at specific ages, and comment on drift that has occurred in the development of pathology in this line since its development 20 years ago. This modern characterization of the 3xTg-AD model includes an assessment of impairments in long-term potentiation followed by quantification of amyloid beta (Aβ) plaque burden and neurofibrillary tau tangles, biochemical levels of Aβ and tau protein, and neuropathological markers such as gliosis and accumulation of dystrophic neurites. We also present a novel comparison of the 3xTg-AD model with the 5xFAD model using the same deep-phenotyping characterization pipeline and show plasma NfL is strongly driven by plaque burden. The results from these analyses are freely available via the AD Knowledge Portal (https://modeladexplorer.org/). Our work demonstrates the utility of a characterization pipeline that generates robust and standardized information relevant to investigating and comparing disease etiologies of current and future models of AD.
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影响因子：
15.1
作者：
Sadleir KR;Eimer WA;Cole SL;Vassar R
通讯作者：
Vassar R
3XTG-AD转基因小鼠的胆碱营养基础前脑系统改变。
影响因子：
6.1
作者：
Perez, Sylvia E.;He, Bin;Muhammad, Nadeem;Oh, Kwang-Jin;Fahnestock, Margaret;Ikonomovic, Milos D.;Mufson, Elliott J.
通讯作者：
Mufson, Elliott J.
DOI：
10.1084/jem.20200861
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthélemy NR;Horie K;Sato C;Bateman RJ
通讯作者：
Bateman RJ
影响因子：
3.7
作者：
Bories C;Guitton MJ;Julien C;Tremblay C;Vandal M;Msaid M;De Koninck Y;Calon F
通讯作者：
Calon F
DOI：
10.1111/neup.12144
发表时间：
2015-02
期刊：
Neuropathology : official journal of the Japanese Society of Neuropathology
影响因子：
--
作者：
Kuninaka N;Kawaguchi M;Ogawa M;Sato A;Arima K;Murayama S;Saito Y
通讯作者：
Saito Y