Localization of human serum amyloid P component and heparan sulfate proteoglycan in in vitro-formed Abeta fibrils

Ultrastructural studies of the localization of serum amyloid P component (SAP) in amyloid fibrils have given divergent results. We here report for the first time that electron microscopy of SAP coincubated with Abeta1-42 peptides or with mature Abeta1-42 fibrils, revealed SAP molecules coating the surface of the mature fibrils and that protofibrils of Abeta1-42 did not bind SAP. Also when incubated with extracted amyloid light chain (AL)-fibrils the SAP molecules aligned on the fibril surface. Heparan sulfate proteoglycan bound to the surface of the Abeta fibrils with a spacing of about 50 nm. We conclude that SAP does not bind to protofibrils but to the surface of mature Abeta fibrils and that it may stabilize and protect the fibrils.