Further evidence of local ganglioside-dependent amyloid beta-protein assembly in brain.
We investigated the molecular mechanism underlying the region-specific deposition of amyloid beta-protein in brains affected with Alzheimer's disease or cerebral amyloid angiopathy. Here, we show that a hereditary variant-type ('Iowa') amyloid beta-protein, which predominantly deposits in the cerebral vessel wall similar to Dutch and Italian-type amyloid beta-proteins, preferably assembles in the presence of GM3 ganglioside. On the basis of our previous findings that first, cerebrovascular smooth muscle cells that provide favorable sites for these variant-type amyloid beta-proteins exclusively express GM3 ganglioside, and second, Dutch and Italian-type amyloid beta-proteins also require GM3 ganglioside for their assembly, our results provide further evidence that local gangliosides play a crucial role in the region-specific amyloid beta-protein deposition in the brain.
Yamamoto
Naoki
N
Department of Alzheimer's Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Japan.
Van Nostrand
William E
WE
Yanagisawa
Katsuhiko
K
D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism; D005732:Gangliosides / Q000737:chemistry*; D006801:Humans; D007202:Indicators and Reagents; D008854:Microscopy, Electron; D009154:Mutation; D012996:Solutions; D013844:Thiazoles / Q000737:chemistry
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005732:Gangliosides; D007202:Indicators and Reagents; D012996:Solutions; D013844:Thiazoles; C009462:thioflavin T