Interaction between amyloid beta-protein aggregates and membranes.
The conversion of soluble, nontoxic amyloid beta-protein (Abeta) to aggregated, toxic Abeta rich in beta-sheet structures is considered to be the key step in the development of Alzheimer's disease. Therefore, extensive studies have been carried out on the mechanisms involved in Abeta aggregation and the characterization of Abeta aggregates formed in aqueous solutions mimicking biological fluids. On the other hand, several investigators pointed out that membranes play an important role in Abeta aggregation. However, it remains unclear whether Abeta aggregates formed in solution and membranes are identical and whether the former can bind to membranes. In this study, using a dye-labeled Abeta-(1-40) as well as native Abeta-(1-40), the properties of Abeta aggregates formed in buffer and raft-like membranes composed of monosialoganglioside GM1/cholesterol/sphingomyelin were compared. Fourier transform infrared spectroscopic measurements suggested that Abeta aggregates formed in buffer and in membranes have different beta-sheet structures. Fluorescence experiments revealed that Abeta aggregated in buffer did not show any affinity for membranes.
Kakio
Atsuko
A
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Yano
Yoshiaki
Y
Takai
Denshi
D
Kuroda
Yukihiro
Y
Matsumoto
Osamu
O
Kozutsumi
Yasunori
Y
Matsuzaki
Katsumi
K
D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002784:Cholesterol; D019281:Dimerization; D005677:G(M1) Ganglioside; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013109:Sphingomyelins
D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments; D013109:Sphingomyelins; D005677:G(M1) Ganglioside; D002784:Cholesterol