Evidence of the existence of micelles in the fibrillogenesis of beta-amyloid peptide.
Alzheimer's disease (AD) is characterized by the deposition of fibrillar deposits formed by the amyloid beta (Abeta) peptide. The most widely accepted model of fibrillogenesis of Abeta affirms that fibrillogenesis occurs in two distinct stages, nucleation and elongation. A modification of the model includes the formation of micelles. We have demonstrated with accurate experimental determinations the existence of aggregates with micellar properties (namely, the critical micellar concentration, CMC, and aggregation number). Values of the CMC were obtained by analysis of surface tension (17.5 microM) and changes in the fluorescence of pyrene (17.6 microM), respectively. The average aggregation number determined by fluorescence quenching was 25, and it was independent of peptide concentration. The presence of micelles implies that above the CMC all excess peptide is incorporated into micelles, and consequently, the monomer concentration is kept almost constant. Thus, micelles act as a peptide reservoir. Micelles are located on-pathway, since they serves as nucleation centers. Experimental data support the model, since above 17.7 microM the time of half-aggregation is independent of peptide concentration, and the overall reaction of the conversion of monomer peptide into fibril can be treated as an apparent first-order reaction.
Sabaté
Raimon
R
Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Avda. Joan XXIII s/n, 08028 Barcelona, Catalonia, Spain.
Estelrich
Joan
J
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001703:Biophysics / Q000379:methods; D002627:Chemistry, Physical / Q000379:methods; D019281:Dimerization; D008823:Micelles; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
D000682:Amyloid; D016229:Amyloid beta-Peptides; D008823:Micelles; D010455:Peptides