title: A seed for Alzheimer amyloid in the brain.
abstract: A fundamental question about the early pathogenesis of Alzheimer's disease (AD) concerns how toxic aggregates of amyloid beta protein (Abeta) are formed from its nontoxic soluble form. We hypothesized previously that GM1 ganglioside-bound Abeta (GAbeta) is involved in the process. We now examined this possibility using a novel monoclonal antibody raised against GAbeta purified from an AD brain. Here, we report that GAbeta has a conformation distinct from that of soluble Abeta and initiates Abeta aggregation by acting as a seed. Furthermore, GAbeta generation in the brain was validated by both immunohistochemical and immunoprecipitation studies. These results imply a mechanism underlying the onset of AD and suggest that an endogenous seed can be a target of therapeutic strategy.
authors.affiliation: Department of Dementia Research, National Institute for Longevity Sciences, Obu 474-8522, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kimura
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Yokoseki
authors.forename: Masao
authors.initials: M
authors.lastname: Shibata
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Michikawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.forename: Katsumi
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: Hironobu
authors.initials: H
authors.lastname: Naiki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanagisawa
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000918:Antibody Specificity; D052160:Benzothiazoles; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008252:Macaca fascicularis; D046911:Macromolecular Substances; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D008081:Liposomes; D046911:Macromolecular Substances; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C009462:thioflavin T; D005677:G(M1) Ganglioside