INCREASED BETA-AMYLOID RELEASE AND LEVELS OF AMYLOID PRECURSOR PROTEIN (APP) IN FIBROBLAST CELL-LINES FROM FAMILY MEMBERS WITH THE SWEDISH ALZHEIMERS-DISEASE APP670/671 MUTATION
INCREASED BETA-AMYLOID RELEASE AND LEVELS OF AMYLOID PRECURSOR PROTEIN (APP) IN FIBROBLAST CELL-LINES FROM FAMILY MEMBERS WITH THE SWEDISH ALZHEIMERS-DISEASE APP670/671 MUTATION
复制标题
DOI：
10.1016/0014-5793(94)01137-0
复制
发表时间：
1994-11-14
期刊：
影响因子：
3.5
通讯作者：
ONEILL, C
中科院分区：
文献类型：
--
作者：
JOHNSTON, JA;COWBURN, RF;ONEILL, C
转染瑞典阿尔茨海默氏病淀粉样前体蛋白APP 670/671突变的细胞系比野生型细胞释放更多的β-淀粉样蛋白。Citron等人[Proc.Natl. Acad. Sci. USA（1994）in press]最近表明，携带APP 670/671突变的成纤维细胞也比对照细胞释放更多的β-淀粉样蛋白[1]。目前的研究证实了一个案例。从携带突变的成纤维细胞释放β-淀粉样蛋白增加三倍。APP mRNA水平没有差异突变轴承和对照细胞，虽然突变轴承成纤维细胞含有显着更多的APP 751/770比对照组。在所有细胞系中，轻度应激降低β-淀粉样蛋白分泌并增加APP 751/770水平。总之，在具有APP 670/671突变的家族成员的成纤维细胞中，致力于淀粉样蛋白形成加工的APP比例增加，并且该突变也可能损害APP应激反应。
Cell lines transfected with the Swedish Alzheimer's disease amyloid precursor protein APP670/671 mutation release significantly more beta-amyloid than wild-type cells. Citron et al. [Proc. Natl. Acad. Sci. USA (1994) in press] have recently shown that fibroblasts carrying the APP670/671 mutation also release more beta-amyloid than control cells [1]. The present study confirms a ca. threefold increase in beta-amyloid release from mutation-bearing fibroblasts. APP mRNA levels did not differ between mutation-bearing and control cells, although mutation-bearing fibroblasts contained significantly more APP751/770 than controls. Mild stress decreased beta-amyloid secretion and increased APP751/770 levels in all cell lines. In conclusion, the proportion of APP committed to amyloidogenic processing is increased in fibroblasts from family members with the APP670/671 mutation, and this mutation may also compromise the APP stress response.