INHIBITION OF ALZHEIMER BETA-PEPTIDE FIBRIL FORMATION BY SERUM AMYLOID-P COMPONENT

A 39-43-amino acid residue-long fragment (beta-peptide) from the amylo id precursor protein is the predominant component of amyloid deposits in the brain of individuals with Alzheimer's disease, Serum amyloid P component (SAP) is present in all types of amyloid, including that of Alzheimer's disease, We have used an in vitro model to study the effec ts of purified SAP on the fibril formation of synthetic Alzheimer beta -peptide 1-42, SAP was found to inhibit fibril formation and to increa se the solubility of the peptide in a dose-dependent manner, At a 5:1 molar ratio of A beta 1-42 peptide to SAP, fibril formation was comple tely inhibited, and approximately 80% of the peptide remained in solut ion even after 4 days of incubation, At lower SAP concentrations, e,g, at peptide to SAP ratio of 1000:1, short fibrillar like structures, l acking amyloid characteristics, were formed, These structures frequent ly contained associated SAP molecules, suggesting that SAP binds to th e polymerizing peptide in a reaction which prevented further fibril fo rmation.