High levels of amyloid-beta protein from S182 (Glu246) familial Alzheimer's cells.
Most early-onset familial Alzheimer disease is associated with missense mutations in S182, a membrane protein on chromosome 14. We investigated amyloid-beta protein (A beta) precursor (A beta PP) metabolism in skin fibroblasts from S182 (Glu246)-affected individuals and unaffected family members. Steady-state A beta PP levels were similar among all lines as was the degree of increase in soluble A beta PP released upon stimulation of cells with either phorbol ester or serum. Among all lines studied, A beta levels were consistently detectable only in the medium of a single line of S182 (Glu246) cells, consistent with the conclusion that some S182 mutant lines may accumulate A beta in their conditioned media. Studies of cells from additional individuals and under other conditions will be required to establish this association of elevated A beta levels with S182 mutations.
Martins
R N
RN
Department of Neurology and Neuroscience, Cornell University Medical College, New York NY 10021, USA.
Turner
B A
BA
Carroll
R T
RT
Sweeney
D
D
Kim
K S
KS
Wisniewski
H M
HM
Blass
J P
JP
Gibson
G E
GE
Gandy
S
S
D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001790:Blood Physiological Phenomena; D016022:Case-Control Studies; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D017354:Point Mutation; D053764:Presenilin-1; D012867:Skin / Q000166:cytology / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D015240:Phorbol 12,13-Dibutyrate