Increased β‐amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the Swedish Alzheimer's disease APP670/671 mutation

FEBS Letters

Norgren, Svante¹  Schenk, Dale⁴  Cowburn, Richard F.³  Johnston, Janet A.³  Venizelos, Nikolaos²  Winblad, Bengt³  O'Neill, Cora³  Vigo-Pelfrey, Carmen⁴  Wiehager, Birgitta³  Lannfelt, Lars³ 

[1] Department of Clinical Genetics, Karolinska Hospital, 104 01 Stockholm, Sweden;Department of Clinical Chemistry, Huddinge Hospital, 141 86 Huddinge, Sweden;Department of Geriatric Medicine, Karolinska Institute, Novum KFC, 141 86 Huddinge, Sweden;Athena Neurosciences Inc., 800F Gateway Boulevard, South San Francisco, CA 94080, USA

关键词: Alzheimer's disease;    Amyloid precursor protein;    APP mRNA;    β-Amyloid;    Fibroblast;    Foetal calf serum;   

DOI  :  10.1016/0014-5793(94)01137-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Cell lines transfected with the Swedish Alzheimer's disease amyloid precursor protein APP670/671 mutation release significantly more β-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 β-amyloid than control cells [1]. The present study confirms a ca. threefold increase in β-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 β-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.

【 授权许可】

Unknown