载脂蛋白E
转基因小鼠
基因敲除
转基因
表型
生物
淀粉样蛋白(真菌学)
淀粉样前体蛋白
基因剔除小鼠
基因型
BACE1-AS系列
细胞外
阿尔茨海默病
细胞生物学
疾病
分子生物学
遗传学
病理
基因
医学
植物
作者
Yoshiko Takebayashi,Yu Yamazaki,Hidetada Yamada,Kyosuke Yazawa,Masahiro Nakamori,Takashi Kurashige,Hiroyuki Morino,Tetsuya Takahashi,Yusuke Sotomaru,Hirofumi Maruyama
标识
DOI:10.1016/j.bbrc.2023.10.038
摘要
Apolipoprotein E4 (APOE4), the strongest risk factor for late-onset Alzheimer's disease (AD), has been revealed to cause greater accumulation of extracellular amyloid β (Aβ) aggregates than does APOE3 in traditional transgenic mouse models of AD. However, concerns that the overexpression paradigm might have affected the phenotype remain. Amyloid precursor protein (APP)-knock-in (KI) mice, incorporating APP mutations associated with AD development, offer an alternative approach for overproducing pathogenic Aβ without needing overexpression of APP. Here, we present the results of comprehensive analyses of pathological and biochemical traits in the brains of APP-KI mice harboring APP-associated familial AD mutations (APPNL-G-F/NL-G-F mice) crossed with human APOE-KI mice. Immunohistochemical and biochemical analyses revealed the APOE genotype-dependent increase in Aβ pathology and glial activation, which was evident within 8 months in the mouse model. These results suggested that this mouse model may be valuable for investigating APOE pathobiology within a reasonable experimental time frame. Thus, this model can be considered in investigating the interaction between APOE and Aβ in vivo, which may not be addressed appropriately by using other transgenic mouse models.
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