A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease
A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease
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DOI：
10.1038/35050103
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发表时间：
2000-12-21
期刊：
影响因子：
64.8
通讯作者：
Morris, RGM
中科院分区：
文献类型：
--
作者：
Chen, GQ;Chen, KS;Morris, RGM
过度表达人类突变淀粉样前体蛋白(HAPP)的小鼠表现出学习障碍，但这些缺陷与HAPP小鼠表现出的进行性β淀粉样斑块形成之间明显缺乏联系是令人费解的。在水迷宫中(1)，HAPP小鼠在淀粉样斑块沉积前后受到损害(2-7)。在这里，我们使用一种新的水迷宫训练方案显示，PDAPP小鼠(8)在学习一系列空间位置方面也表现出与年龄相关的单独缺陷。这种损害与b-淀粉样斑块负荷相关，在横断面和纵向实验设计中都有表现。线索导航和物体识别记忆是正常的。这些发现表明，抗体过度表达和/或抗体斑块与认知功能障碍有关，重要的是，一些但不是所有形式的学习和记忆是与阿尔茨海默病类型的病理相关的进行性认知缺陷的合适的行为分析。
;Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta -amyloid plaque formation that the hAPP mice display is puzzling. In the water maze(1), hAPP mice are impaired before and after amyloid plaque deposition(2-7). Here we show, using a new water-maze training protocol, that PDAPP mice(8) also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with b-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that Ab overexpression and/or Ab plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies.