Moran P M, Higgins L S, Cordell B, Moser P C
Marion Merrell Dow Research Institute, Strasbourg, France.
Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5341-5. doi: 10.1073/pnas.92.12.5341.
The beta-amyloid precursor protein (beta-APP), from which the beta-A4 peptide is derived, is considered to be central to the pathogenesis of Alzheimer disease (AD). Transgenic mice expressing the 751-amino acid isoform of human beta-APP (beta-APP751) have been shown to develop early AD-like histopathology with diffuse deposits of beta-A4 and aberrant tau protein expression in the brain, particularly in the hippocampus, cortex, and amygdala. We now report that beta-APP751 transgenic mice exhibit age-dependent deficits in spatial learning in a water-maze task and in spontaneous alternation in a Y maze. These deficits were mild or absent in 6-month-old transgenic mice but were severe in 12-month-old transgenic mice compared to age-matched wild-type control mice. No other behavioral abnormalities were observed. These mice therefore model the progressive learning and memory impairment that is a cardinal feature of AD. These results provide evidence for a relationship between abnormal expression of beta-APP and cognitive impairments.
β-淀粉样前体蛋白（β-APP）是β-A4肽的来源，被认为是阿尔茨海默病（AD）发病机制的核心。已表明，表达人β-APP 751氨基酸异构体（β-APP751）的转基因小鼠会出现早期AD样组织病理学变化，大脑中尤其是海马体、皮质和杏仁核出现β-A4的弥漫性沉积以及异常的tau蛋白表达。我们现在报告，β-APP751转基因小鼠在水迷宫任务中的空间学习和Y迷宫中的自发交替行为方面表现出年龄依赖性缺陷。与年龄匹配的野生型对照小鼠相比，这些缺陷在6个月大的转基因小鼠中较轻或不存在，但在12个月大的转基因小鼠中很严重。未观察到其他行为异常。因此，这些小鼠模拟了作为AD主要特征的进行性学习和记忆障碍。这些结果为β-APP异常表达与认知障碍之间的关系提供了证据。
