Inhibition of Alzheimer beta-peptide fibril formation by serum amyloid P component.
A 39-43-amino acid residue-long fragment (beta-peptide) from the amyloid 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 effects of purified SAP on the fibril formation of synthetic Alzheimer beta-peptide 1-42. SAP was found to inhibit fibril formation and to increase 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 completely inhibited, and approximately 80% of the peptide remained in solution even after 4 days of incubation. At lower SAP concentrations, e.g. at peptide to SAP ratio of 1000:1, short fibrillar like structures, lacking amyloid characteristics, were formed. These structures frequently contained associated SAP molecules, suggesting that SAP binds to the polymerizing peptide in a reaction which prevented further fibril formation.
Janciauskiene
S
S
Department of Medicine, Lund University, University Hospital, Malmö, Sweden.
García de Frutos
P
P
Carlemalm
E
E
Dahlbäck
B
B
Eriksson
S
S
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D001921:Brain / Q000378:metabolism; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D006801:Humans; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000737:chemistry; D000685:Serum Amyloid A Protein / Q000302:isolation & purification / Q000494:pharmacology*; D000515:alpha 1-Antitrypsin / Q000187:drug effects / Q000648:ultrastructure
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D000685:Serum Amyloid A Protein; D000515:alpha 1-Antitrypsin