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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Age Factors
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Aged
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Aged, 80 and over
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Alzheimer Disease / etiology
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Alzheimer Disease / metabolism*
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Alzheimer Disease / pathology
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Amyloid / biosynthesis*
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Amyloid / chemistry
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Amyloid beta-Peptides / chemistry
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / toxicity
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Animals
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Antibody Specificity
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Benzothiazoles
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Brain / metabolism*
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Brain / pathology
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Brain Chemistry
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Cell Survival / drug effects
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Cells, Cultured
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G(M1) Ganglioside / chemistry
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G(M1) Ganglioside / metabolism
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Humans
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Liposomes / chemistry
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Macaca fascicularis
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Macromolecular Substances
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Microscopy, Immunoelectron
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Middle Aged
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Neurons / drug effects
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Neurons / metabolism*
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Neurons / pathology
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Peptide Fragments / toxicity
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Rats
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Rats, Sprague-Dawley
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Thiazoles / chemistry
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Thiazoles / metabolism
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Time Factors
Substances
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Amyloid
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Amyloid beta-Peptides
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Benzothiazoles
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Liposomes
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Macromolecular Substances
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Peptide Fragments
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Thiazoles
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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thioflavin T
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G(M1) Ganglioside