Neurologic and motor dysfunctions in APP transgenic mice.
Neurologic and motor dysfunctions in APP transgenic mice.
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DOI：
10.1515/revneuro-2012-0041
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发表时间：
2012
影响因子：
4.1
通讯作者：
Strazielle C
中科院分区：
文献类型：
--
作者：
Lalonde R;Fukuchi K;Strazielle C
常染色体显性遗传性阿尔茨海默病基因突变的发现使研究人员能够在转基因小鼠身上复制这种疾病的几个特征，特别是大脑中Aβ斑块的形成和认知缺陷。还对APP转基因突变体的存活率、神经功能和运动协调进行了研究，这些都是阿尔茨海默病的易感因素。几个表达人突变APP或野生型APP的转基因品系在有或不存在Aβ斑块的情况下，死亡率都高于非转基因对照。有血管淀粉样蛋白积聚的APP转基因小鼠的死亡率也较高，因此在所有APP转基因模型中观察到的早逝与脑血管因素有关。此外，在APP突变体中已经描述了肌阵挛跳跃，以及癫痫活动，异常的肢体屈曲和紧爪反射，以及运动协调缺陷。神经学体征类似于晚期阿尔茨海默病中观察到的肌阵挛运动、癫痫发作、病理反射和步态问题。
The discovery of gene mutations underlying autosomal dominant Alzheimer’s disease has enabled researchers to reproduce several hallmarks of this disorder in transgenic mice, notably the formation of Aβ plaques in brain and cognitive deficits. APP transgenic mutants have also been investigated with respect to survival rates, neurologic functions, and motor coordination, which are all susceptible to alteration in Alzheimer dementia. Several transgenic lines expressing human mutated or wild-type APP had higher mortality rates than non-transgenic controls with or without the presence of Aβ plaques. Mortality rates were also elevated in APP transgenic mice with vascular amyloid accumulation, thereby implicating cerebrovascular factors in the precocious death observed in all APP transgenic models. In addition, myoclonic jumping has been described in APP mutants, together with seizure activity, abnormal limb-flexion and paw-clasping reflexes, and motor coordination deficits. The neurologic signs resemble the myoclonic movements, epileptic seizures, pathological reflexes, and gait problems observed in late-stage Alzheimer’s disease.
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