CELLS WITH A FAMILIAL ALZHEIMERS-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 (Abeta). Because these findings were based on immunological identification, we have chemically characterized the peptides produced. Purified Abeta fragments from the conditioned media of these cells were found to have N-terminal sequence consistent with the Abeta found in cerebral plaques. Mass spectrometric data demonstrated a series of Abeta fragments consistent with those found in Alzheimer's disease (AD); the major species corresponding to Abeta(1-40). Significantly, a longer fragment corresponding to Abeta(1-42) was found. These findings suggest that this cellular system may be useful for mechanistic studies of Abeta generation and possibly for the development of therapeutic agents to treat AD.