POTENTIALLY AMYLOIDOGENIC, CARBOXYL-TERMINAL DERIVATIVES OF THE AMYLOID PROTEIN-PRECURSOR

The 39- to 43-amino acid amyloid beta-protein (beta-AP), which is deposited as amyloid in Alzheimer's disease, is encoded as an internal peptide that begins 99 residues from the carboxyl terminus of a 695- to 770-amino acid glycoprotein referred to as the amyloid beta-protein precursor (beta-APP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the beta-APP were analyzed. This analysis showed that the beta-APP is normally processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives. The two largest derivatives in human brain have the entire beta-AP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition.