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首页> 外文期刊>Neuron >Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction.
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Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction.

机译：具有斑块和缠结的阿尔茨海默氏病三重转基因模型：细胞内Abeta和突触功能障碍。

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摘要

The neuropathological correlates of Alzheimer's disease (AD) include amyloid-beta (Abeta) plaques and neurofibrillary tangles. To study the interaction between Abeta and tau and their effect on synaptic function, we derived a triple-transgenic model (3xTg-AD) harboring PS1(M146V), APP(Swe), and tau(P301L) transgenes. Rather than crossing independent lines, we microinjected two transgenes into single-cell embryos from homozygous PS1(M146V) knockin mice, generating mice with the same genetic background. 3xTg-AD mice progressively develop plaques and tangles. Synaptic dysfunction, including LTP deficits, manifests in an age-related manner, but before plaque and tangle pathology. Deficits in long-term synaptic plasticity correlate with the accumulation of intraneuronal Abeta. These studies suggest a novel pathogenic role for intraneuronal Abeta with regards to synaptic plasticity. The recapitulation of salient features of AD in these mice clarifies the relationships between Abeta, synaptic dysfunction, andtangles and provides a valuable model for evaluating potential AD therapeutics as the impact on both lesions can be assessed.
机译：阿尔茨海默氏病（AD）的神经病理学相关因素包括淀粉样蛋白（Abeta）斑块和神经原纤维缠结。若要研究Abeta和tau之间的相互作用及其对突触功能的影响，我们推导了一个包含PS1（M146V），APP（Swe）和tau（P301L）转基因的三重转基因模型（3xTg-AD）。而不是跨越独立的系，我们将两个转基因从纯合PS1（M146V）基因敲入小鼠的单细胞胚胎中显微注射，生成具有相同遗传背景的小鼠。 3xTg-AD小鼠逐渐形成斑块和缠结。包括LTP缺陷在内的突触功能障碍与年龄相关，但在斑块和缠结病理之前出现。长期突触可塑性的缺陷与神经内Abeta的积累有关。这些研究表明神经内Abeta关于突触可塑性的新型致病作用。在这些小鼠中AD的显着特征的概括阐明了Abeta，突触功能障碍和缠结之间的关系，并为评估潜在的AD疗法提供了有价值的模型，因为可以评估对两种病变的影响。

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