Assembly of hereditary amyloid beta-protein variants in the presence of favorable gangliosides.
The mechanisms underlying regional amyloid beta-protein (Abeta) deposition in brain remain unclear. Here we show that assembly of hereditary variant Dutch- and Italian-type Abetas, and Flemish-type Abeta was accelerated by GM3 ganglioside, and GD3 ganglioside, respectively. Notably, cerebrovascular smooth muscle cells, which compose the cerebral vessel wall at which the Dutch- and Italian-type Abetas deposit, exclusively express GM3 whereas GD3 is upregulated in the co-culture of endothelial cells and astrocytes, which forms the cerebrovascular basement membrane, the site of Flemish-type Abeta deposition. Our results suggest that regional Abeta deposition is induced by the local gangliosides in the brain.
Yamamoto
Naoki
N
Department of Alzheimer's Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Obu 474-8522, Japan.
Hirabayashi
Yoshio
Y
Amari
Masakuni
M
Yamaguchi
Haruyasu
H
Romanov
Galina
G
Van Nostrand
William E
WE
Yanagisawa
Katsuhiko
K
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry
D016229:Amyloid beta-Peptides; D005732:Gangliosides