Environment- and mutation-dependent aggregation behavior of Alzheimer amyloid beta-protein.
The deposition of amyloid beta-protein in the brain is a fundamental process in the development of Alzheimerís disease; however, the mechanism underlying aggregation of amyloid beta-protein remains to be determined. Here, we report that a membrane-mimicking environment, generated in the presence of detergents or a ganglioside, is sufficient per se for amyloid fibril formation from soluble amyloid beta-protein. Furthermore, hereditary variants of amyloid beta-protein, which are caused by amyloid precursor protein gene mutations, including the Dutch (E693Q), Flemish (A692G) and Arctic (E693G) types, show mutually different aggregation behavior in these environments. Notably, the Arctic-type amyloid beta-protein, in contrast to the wild-type and other variant forms, shows a markedly rapid and higher level of amyloid fibril formation in the presence of sodium dodecyl sulfate or GM1 ganglioside. These results suggest that there are favorable local environments for fibrillogenesis of amyloid beta-protein.
Yamamoto
Naoki
N
Department of Dementia Research, National Institute for Longevity Sciences, Obu, Japan.
Hasegawa
Kazuhiro
K
Matsuzaki
Katsumi
K
Naiki
Hironobu
H
Yanagisawa
Katsuhiko
K
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002942:Circular Dichroism; D003902:Detergents / Q000737:chemistry / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008567:Membranes, Artificial; D008854:Microscopy, Electron; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary / Q000187:drug effects
D016229:Amyloid beta-Peptides; D003902:Detergents; D046911:Macromolecular Substances; D008567:Membranes, Artificial; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D005677:G(M1) Ganglioside