title: Role of glycosylation in hyperphosphorylation of tau in Alzheimer's disease.
abstract: In Alzheimer's disease (AD) brain, microtubule-associated protein tau is abnormally modified by hyperphosphorylation and glycosylation, and is aggregated as neurofibrillary tangles of paired helical filaments. To investigate the role of tau glycosylation in neurofibrillary pathology, we isolated various pools of tau protein from AD brain which represent different stages of tau pathology. We found that the non-hyperphosphorylated tau from AD brain but not normal brain tau was glycosylated. Monosaccharide composition analyses and specific lectin blots suggested that the tau in AD brain was glycosylated mainly through N-linkage. In vitro phosphorylation indicated that the glycosylated tau was a better substrate for cAMP-dependent protein kinase than the deglycosylated tau. These results suggest that the glycosylation of tau is an early abnormality that can facilitate the subsequent abnormal hyperphosphorylation of tau in AD brain.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Tanweer
authors.initials: T
authors.lastname: Zaidi
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: Roberta K
authors.initials: RK
authors.lastname: Merkle
authors.forename: Cheng Xin
authors.initials: CX
authors.lastname: Gong
mesh_terms: D000117:Acetylglucosamine / Q000032:analysis; D000544:Alzheimer Disease / Q000209:etiology*; D006031:Glycosylation; D006601:Hexoses / Q000032:analysis; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000032:analysis; D016874:Neurofibrillary Tangles; D009713:Nucleotidyltransferases / Q000032:analysis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006601:Hexoses; D016875:tau Proteins; D009713:Nucleotidyltransferases; C023226:UDPacetylglucosamine pyrophosphorylase; D019158:N-Acetylneuraminic Acid; D000117:Acetylglucosamine