Identification and characterization of C-terminal fragments of the beta-amyloid precursor produced in cell culture.

The mechanism of amyloid formation in Alzheimer's disease is unknown but appears to involve proteolytic processing of the amyloidogenic peptide from a larger precursor. When the C-terminus containing the amyloid-forming and cytoplasmic domains of the precursor was recombinantly expressed in cultured mammalian cells, a 16 kd protein accumulated which had a tendency to aggregate and form deposits. These deposits had physical characteristics resembling those of preamyloid. Recombinant expression of the full-length precursor was found to produce a similar, cell-associated 16 kd C-terminal fragment as well as a 12 kd fragment, neither of which formed detectable aggregates suggesting efficient catabolism of these fragments. Identification of these two naturally occurring metabolic products of the beta-amyloid precursor provides a system permitting the characterization of the proteolytic processing events of the amyloid precursor protein.