AGE-RELATED CNS DISORDER AND EARLY DEATH IN TRANSGENIC FVB/N MICE OVEREXPRESSING ALZHEIMER AMYLOID PRECURSOR PROTEINS
AGE-RELATED CNS DISORDER AND EARLY DEATH IN TRANSGENIC FVB/N MICE OVEREXPRESSING ALZHEIMER AMYLOID PRECURSOR PROTEINS
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DOI：
10.1016/0896-6273(95)90107-8
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发表时间：
1995-11-01
期刊：
影响因子：
16.2
通讯作者：
CARLSON, G
中科院分区：
文献类型：
--
作者：
HSIAO, KK;BORCHELT, DR;CARLSON, G
过量表达人(Hu)或小鼠(Mo)阿尔茨海默病淀粉样前体蛋白(APP(695))的转基因FVB/N小鼠过早死亡，并发展成一种中枢神经系统疾病，包括新的恐惧症和空间变换障碍，葡萄糖利用降低，星形胶质细胞增多，主要分布在大脑。新恐惧症的发病年龄和死亡年龄随着脑APP水平的增加而降低。HuAPP转基因比类似水平表达的MoAPP转基因更早导致死亡。NA胞外淀粉样蛋白被检测到，表明与APP过度表达有关的一些有害过程与淀粉样蛋白的形成无关。接近20%的非转基因小鼠在成年中后期自发出现类似的临床症状，这表明APP的过度表达可能会加速FVB/N小鼠自然发生的与年龄相关的中枢神经系统疾病。
Transgenic FVB/N mice overexpressing human (Hu) or mouse (Mo) Alzheimer amyloid precursor protein (APP(695)) die early and develop a CNS disorder that includes neophobia and impaired spatial alternation, with diminished glucose utilization and astrogliosis mainly in the cerebrum. Age at onset of neophobia and age at death decrease with increasing levers of brain APP. HuAPP transgenes induce death much earlier than MoAPP transgenes expressed at similar levels. Na extracellular amyloid was detected, indicating that some deleterious processes related to APP overexpression are dissociated from formation of amyloid. A similar clinical syndrome occurs spontaneously in similar to 20% of nontransgenic mice when they reach mid- to late-adult life, suggesting that APP overexpression may accelerate a naturally occuring age-related CNS disorder in FVB/N mice.