title: Glycosylation of microtubule-associated protein tau in Alzheimer's disease brain.
abstract: In the neurofibrillary pathology of Alzheimer's disease (AD), neurofibrillary tangles (NFTs) contain paired helical filaments (PHFs) as their major fibrous component. Abnormally hyperphosphorylated, microtubule-associated protein tau is the major protein subunit of PHFs. A recent in vitro study showed that PHF tangles from AD brains are highly glycosylated, whereas no glycan is detected in normal tau. Deglycosylation of PHF tangles converts them into bundles of straight filaments and restores their accessibility to microtubules. We showed that PHF tangles from AD brain tissue were associated with specific glycan molecules by double immunostaining with peroxidase and alkaline phosphatase labeling. Intracellular tangles and dystrophic neurites in a neuritic plaque with abnormally hyperphosphorylated tau, detected with the monoclonal antibodies AT-8 and anti-tau-2, were also positive with lectin Galanthus nivalis agglutinin (GNA) which recognizes both the N- and O-glycosidically linked saccharides. Colocalization was not seen in the extracellular tangles and amyloid deposition, suggesting that the glycosylation of tau might be associated with the early phase of insoluble NFT formation. Thus, although abnormal phosphorylation might promote aggregation of tau and inhibition of the assembly of microtubules, glycosylation mediated by a GNA-positive glycan appears to be responsible for the formation of the PHF structures in vivo.
authors.affiliation: Department of Internal Medicine and Health Care, School of Medicine, Fukuoka University, Japan. mm039012@msat.fukuoka-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Tsujioka
authors.forename: T
authors.initials: T
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: H
authors.initials: H
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Z
authors.initials: Z
authors.lastname: Liposits
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism*; D027801:Galanthus; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D016875:tau Proteins