Gangliosides determine the amyloid pathology of Alzheimer's disease.
Gangliosides, GM3 and GM1, are suggested to accelerate the deposition of the amyloid beta-protein as amyloid angiopathy and senile plaques, respectively, in the Alzheimer brain. We investigated the profile of amyloid deposition in the brains of transgenic mice expressing a mutant amyloid precursor protein with a disrupted GM2 synthase gene, in which GM3 accumulates whereas GM1 is lacking. These mice showed a significantly increased level of deposited amyloid beta-protein in the vascular tissues. Furthermore, formation of severe dyshoric-form amyloid angiopathy, in which amyloid extended from the blood vessel walls deeply into the surrounding parenchyma was observed. Our results indicate that the expression of gangliosides is a critical determinant for the amyloid pathology in the Alzheimer brain.
Oikawa
Naoto
N
Department of Alzheimer's Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Morioka, Obu, Japan.
Yamaguchi
Haruyasu
H
Ogino
Koichi
K
Taki
Takao
T
Yuyama
Kohei
K
Yamamoto
Naoki
N
Shin
Ryong-Woon
RW
Furukawa
Koichi
K
Yanagisawa
Katsuhiko
K
D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism / Q000473:pathology; D005677:G(M1) Ganglioside / Q000172:deficiency / Q000378:metabolism*; D005679:G(M3) Ganglioside / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005679:G(M3) Ganglioside; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D005677:G(M1) Ganglioside; D017350:N-Acetylgalactosaminyltransferases; C023220:(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase