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/

Cell lines transfected with the Swedish Alzheimer's disease amyloid pr ecursor protein APP670/671 mutation release significantly more beta-am yloid than wild-type cells. Citron et al. [Proc. Natl. Acad. Sci. USA (1994) in press] have recently shown that fibroblasts carrying the APP 670/671 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 dif fer between mutation-bearing and control cells, although mutation-bear ing 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 commit ted to amyloidogenic processing is increased in fibroblasts from famil y members with the APP670/671 mutation, and this mutation may also com promise the APP stress response.