HUMAN SERUM AMYLOID-P COMPONENT IS AN INVARIANT CONSTITUENT OF AMYLOID DEPOSITS AND HAS A UNIQUELY HOMOGENEOUS GLYCOSTRUCTURE

Human serum amyloid P component (SAP) is a normal plasma protein and t he precursor of amyloid P component (AP), a universal constituent of t he abnormal tissue deposits in amyloidosis, including Alzheimer diseas e. We show here that its single N-linked biantennary oligosaccharide d oes not display the microheterogeneity usually characteristic of glyco proteins. The protein and the glycan structures of AP were also invari ant, their resistance to degradation suggesting a role in persistence of amyloid deposits. Asialo-SAP was rapidly cleared from the circulati on in mice by a mechanism dependent on terminal galactose residues and was catabolized in hepatocytes. However blockade of this pathway did not affect the clearance of native SAP. Rapid hepatic uptake and catab olism of human asialo-SAP in man were also directly demonstrated. The protein and glycan homogeneity of SAP and the integrity of AP suggest that the complete glycoprotein structure is important for the normal a nd the pathophysiological functions of this molecule.