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首页> 外文期刊>The European Journal of Neuroscience >Age-dependent cognitive decline in the APP23 model precedes amyloid deposition.
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Age-dependent cognitive decline in the APP23 model precedes amyloid deposition.

机译：APP23模型中年龄相关的认知功能下降先于淀粉样蛋白沉积。

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Heterozygous APP23 mice, expressing human amyloid-precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6-8 weeks, 3 and 6 months. A hidden-platform Morris-type water maze showed an age-dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage-activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2-h recording during dusk phase demonstrated lower activity levels in 6-month-old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open-field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque-associated human amyloid-beta 1-42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque-associated amyloid-beta 1-42 peptides, but probe trial performance did correlate negatively with soluble amyloid-beta brain concentration in 3-month-old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.
机译：表达具有瑞典双突变和对照同窝仔的人淀粉样前体蛋白的杂合APP23小鼠在6-8周，3和6个月大时接受行为和神经运动任务。一个隐藏平台的莫里斯型水迷宫在APP23模型中显示出与年龄有关的空间记忆能力下降。从3个月大以后，APP23小鼠显示出严重的学习和记忆障碍，这在采集期间严重受损的学习曲线和受损的探针试验性能中得到了证明。除了认知缺陷外，APP23小鼠还表现出活动模式异常。隔夜笼活动记录显示，在测试的三个年龄组中，转基因动物活动过度。但是，与对照组相比，黄昏阶段短短的2小时记录显示6个月大的APP23小鼠的活动水平较低。而且，在这个年龄，APP23小鼠在野外范例中在探索和活动水平方面与对照同窝仔不同。这些发现让人想起阿尔茨海默氏症患者的昼夜节律和活动紊乱。大脑中与斑块相关的人类淀粉样蛋白1-42肽的测定显示，与年轻的转基因相比，杂合APP23小鼠在6个月时增加了五倍。这种增加与海马和新皮质中斑块的首次出现相吻合。空间记忆缺陷先于斑块形成和与斑块相关的淀粉样β1-42肽增加，但探针试验性能与3个月大的APP23突变体中的可溶性淀粉样β脑浓度呈负相关。可检测到的斑块形成不是（唯一的）导致APP23模型中记忆缺陷的原因。

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