Cells with a familial Alzheimer's disease mutation produce authentic beta-peptide.
Cells overexpressing the beta-amyloid precursor protein possessing a mutation found in familial Alzheimer's disease overproduce beta-amyloid peptide (A beta). Because these findings were based on immunological identification, we have chemically characterized the peptides produced. Purified A beta fragments from the conditioned media of these cells were found to have N-terminal sequence consistent with the A beta found in cerebral plaques. Mass spectrometric data demonstrated a series of A beta fragments consistent with those found in Alzheimer's disease (AD); the major species corresponding to A beta(1-40). Significantly, a longer fragment corresponding to A beta(1-42) was found. These findings suggest that this cellular system may be useful for mechanistic studies of A beta generation and possibly for the development of therapeutic agents to treat AD.
Dovey
H F
HF
Athena Neurosciences, Inc., South San Francisco, California 94080.
Suomensaari-Chrysler
S
S
Lieberburg
I
I
Sinha
S
S
Keim
P S
PS
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002460:Cell Line; D002845:Chromatography; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007158:Immunologic Techniques; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009154:Mutation
D016229:Amyloid beta-Peptides