Abstract
Sulfo-glycosaminoglycans (sGAGs) are involved in the assembly of tau in at least a subpopulation of paired helical filaments (PHFs) in Alzheimer's disease (AD). To further understand the role of sGAG molecules in the structure of PHFs, we isolated PHFs from patients with AD and treated them with heparinase. Immunoelectron microscopy and Western blotting (WB) were used later on to analyze the changes obtained. The heparinase treatment abolished Tau14 and AT8 immunodecoration (two N-terminal tau antibodies) and increased PHF-1 labeling (a C-terminal antibody). In addition, heparinase-treated filaments are more labile than control ones as demonstrated by sodium dodecyl sulfate-extraction and subsequent WB. In summary, our results demonstrate that sGAG content affects PHF conformation as well as PHF-tau solubilization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism*
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Alzheimer Disease / pathology
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Alzheimer Disease / physiopathology
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Amino Acid Sequence / physiology
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Antibodies
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Brain / metabolism*
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Brain / pathology
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Brain / ultrastructure
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Epitopes / chemistry
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Epitopes / immunology
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Glycosaminoglycans / chemistry*
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Heparin Lyase
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Humans
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Immunohistochemistry
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Microscopy, Electron
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Molecular Conformation
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Neurofibrillary Tangles / chemistry*
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Neurofibrillary Tangles / ultrastructure
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Neurons / metabolism*
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Neurons / pathology
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Neurons / ultrastructure
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Protein Isoforms / chemistry
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Protein Isoforms / ultrastructure
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Protein Structure, Tertiary / drug effects
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Protein Structure, Tertiary / physiology
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Solubility
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Sulfuric Acid Esters / chemistry*
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tau Proteins / chemistry*
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tau Proteins / ultrastructure
Substances
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Antibodies
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Epitopes
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Glycosaminoglycans
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Protein Isoforms
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Sulfuric Acid Esters
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tau Proteins
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Heparin Lyase