Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease
Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease
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DOI：
10.1016/j.nbd.2006.08.017
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发表时间：
2006-12-01
影响因子：
6.1
通讯作者：
Frosch, Matthew P.
中科院分区：
文献类型：
--
作者：
Garcia-Alloza, Monica;Robbins, Elissa M.;Frosch, Matthew P.
携带与阿尔茨海默病相关的疾病相关基因的转基因小鼠经常表现出β -淀粉样蛋白沉积，如老年斑和脑淀粉样血管病。我们描述了APPswe/PS1dE9小鼠的β -淀粉样蛋白沉积的自然历史，APPswe/PS1dE9是一种特别具有攻击性的转基因小鼠模型，由突变的APP （APPswe: KM594/5NL）和PS1 （dE9：缺失9外显子）转基因产生。离体组织化学显示A - β沉积4个月，斑块数量逐渐增加至12个月，A - β水平也有类似的增加。体内多光子显微镜每隔一周显示β -淀粉样蛋白沉积增加，如CAA和斑块。尽管CAA首先出现在早期，但其进展速度明显慢于Tg2576小鼠。APPswe/PS1dE9模型中β -淀粉样蛋白积累的一致性和早发性证实了其在研究p -淀粉样蛋白沉积的生化和病理机制以及探索新的治疗方法方面的实用性。(c) 2006爱思唯尔公司版权所有。
Transgenic mice carrying disease-linked forms of genes associated with Alzheimer disease often demonstrate deposition of the beta-amyloid as senile plaques and cerebral amyloid angiopathy. We have characterized the natural history of beta-amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1 (dE9: deletion of exon 9). Ex vivo histochemistry showed A beta deposition by 4 months with a progressive increase in plaque number up to 12 months and a similar increase of A beta levels. In vivo multiphoton microscopy at weekly intervals showed increasing beta-amyloid deposition as CAA and plaques. Although first appearing at an early age, CAA progressed at a significantly slower rate than in the Tg2576 mice. The consistent and early onset of beta-amyloid accumulation in the APPswe/PS1dE9 model confirms its utility for studies of biochemical and pathological mechanisms underlying P-amyloid deposition, as well as exploring new therapeutic treatments. (c) 2006 Elsevier Inc. All rights reserved.