Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor

The 39- to 43-amino acid amyloid β protein (βAP), 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 β protein precursor (βAPP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the βAPP were analyzed. This analysis showed that the βAPP 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 βAP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition.