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

Abstract

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.