Augmented senile plaque load in aged female β-amyloid precursor protein-transgenic mice
Augmented senile plaque load in aged female β-amyloid precursor protein-transgenic mice
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DOI：
10.1016/s0002-9440(10)64064-3
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发表时间：
2001-03-01
影响因子：
6
通讯作者：
Walker, LC
中科院分区：
文献类型：
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作者：
Callahan, MJ;Lipinski, WJ;Walker, LC
过表达具有瑞典突变（APP 695 SWE）的人β-淀粉样前体蛋白的转基因小鼠（Tg 2576）在8至10月龄时产生阿尔茨海默病样淀粉样β蛋白（A β）沉积。这些小鼠显示A β 40和A β 42水平升高，以及大脑中弥漫性和致密性老年斑的年龄相关性增加。在8至19月龄雄性和雌性Tg 2576小鼠的海马和新皮质中定量老年斑块负荷。在所有小鼠中，12月龄后斑块负荷显著增加。在15和19月龄时，雌性小鼠的老年斑负荷明显大于雄性小鼠;在15月龄时研究的31只小鼠中，雌性Tg 2576小鼠的斑块面积几乎是雄性小鼠的3倍。通过酶联免疫吸附测定，雌性小鼠的大脑中A β 40和A β 42也比雄性小鼠多，尽管这种差异不如组织学斑块负荷的差异明显。这些数据表明，衰老的雌性Tg 2576小鼠存款更多的淀粉样蛋白在大脑中比雄性小鼠，并可能提供一种动物模型，其中性别差异对大脑淀粉样蛋白病理学的影响可以进行评估。
Transgenic mice (Tg2576) overexpressing human beta -amyloid precursor protein with the Swedish mutation (APP695SWE) develop Alzheimer's disease-like amyloid beta protein (A beta) deposits by 8 to 10 months of age. These mice show elevated levels of A beta 40 and A beta 42, as well as an age-related increase in diffuse and compact senile plaques in the brain. Senile plaque load was quantitated in the hippocampus and neocortex of 8- to 19-month-old male and female Tg2576 mice. In all mice, plaque burden increased markedly after the age of 12 months. At 15 and 19 months of age, senile plaque load was significantly greater in females than in males; in 31 mice studied at 15 months of age, the area occupied by plaques in female Tg2576 mice was nearly three times that of males. By enzyme-linked immunosorbent assay, female mice also had more A beta 40 and A beta 42 in the brain than did males, although this difference was less pronounced than the difference in histological plaque load. These data show that senescent female Tg2576 mice deposit more amyloid in the brain than do male mice, and may provide an animal model in which the influence of sex differences on cerebral amyloid pathology can be evaluated.