title: Imbalance in fatty-acid-chain length of gangliosides triggers Alzheimer amyloid deposition in the precuneus.
abstract: Amyloid deposition, a crucial event of Alzheimer's disease (AD), emerges in distinct brain regions. A key question is what triggers the assembly of the monomeric amyloid ß-protein (Aß) into fibrils in the regions. On the basis of our previous findings that gangliosides facilitate the initiation of Aß assembly at presynaptic neuritic terminals, we investigated how lipids, including gangliosides, cholesterol and sphingomyelin, extracted from synaptic plasma membranes (SPMs) isolated from autopsy brains were involved in the Aß assembly. We focused on two regions of the cerebral cortex; precuneus and calcarine cortex, one of the most vulnerable and one of the most resistant regions to amyloid deposition, respectively. Here, we show that lipids extracted from SPMs isolated from the amyloid-bearing precuneus, but neither the amyloid-free precuneus nor the calcarine cortex, markedly accelerate the Aß assembly in vitro. Through liquid chromatography-mass spectrometry of the lipids, we identified an increase in the ratio of the level of GD1b-ganglioside containing C20:0 fatty acid to that containing C18:0 as a cause of the enhanced Aß assembly in the precuneus. Our results suggest that the local glycolipid environment play a critical role in the initiation of Alzheimer amyloid deposition.
authors: Department of Drug Discovery, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Aichi, Japan.
authors: Naoto
authors: N
authors: Oikawa
authors: Department of Bioscience and Informatics, Keio University, Kanagawa, Japan.
authors: Teruhiko
authors: T
authors: Matsubara
authors: Department of Bioscience and Informatics, Keio University, Kanagawa, Japan.
authors: Ryoto
authors: R
authors: Fukuda
authors: Department of Bioscience and Informatics, Keio University, Kanagawa, Japan.
authors: Hanaki
authors: H
authors: Yasumori
authors: Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Hatsuta
authors: Department of Neuropathology, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors: Shigeo
authors: S
authors: Murayama
authors: Department of Bioscience and Informatics, Keio University, Kanagawa, Japan.
authors: Toshinori
authors: T
authors: Sato
authors: Institute of Glycoscience, Tokai University, Kanagawa, Japan.
authors: Akemi
authors: A
authors: Suzuki
authors: Department of Drug Discovery, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Aichi, Japan; Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Aichi, Japan.
authors: Katsuhiko
authors: K
authors: Yanagisawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D005227:Fatty Acids; D005732:Gangliosides; D013109:Sphingomyelins; C033851:ganglioside, GD1b; D002784:Cholesterol