Increased beta-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.
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.
Johnston
J A
JA
Department of Geriatric Medicine, Karolinska Institute, Huddinge, Sweden.
Cowburn
R F
RF
Norgren
S
S
Wiehager
B
B
Venizelos
N
N
Winblad
B
B
Vigo-Pelfrey
C
C
Schenk
D
D
Lannfelt
L
L
O'Neill
C
C
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D017077:Culture Media, Conditioned; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D013548:Sweden; D014162:Transfection
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017077:Culture Media, Conditioned; D012333:RNA, Messenger