title: Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress.
abstract: The stability of proteins that constitute the neurofibrillary tangles and senile plaques of Alzheimer disease suggests that they would be ideal substrates for nonenzymatic glycation, a process that occurs over long times, even at normal levels of glucose, ultimately resulting in the formation of advanced glycation end products (AGEs). AGE-modified proteins aggregate, and they generate reactive oxygen intermediates. Using monospecific antibody to AGEs, we have colocalized these AGEs with paired helical filament tau in neurofibrillary tangles in sporadic Alzheimer disease. Such neurons also exhibited evidence of oxidant stress: induction of malondialdehyde epitopes and heme oxygenase 1 antigen. AGE-recombinant tau generated reactive oxygen intermediates and, when introduced into the cytoplasm of SH-SY5Y neuroblastoma cells, induced oxidant stress. We propose that in Alzheimer disease, AGEs in paired helical filament tau can induce oxidant stress, thereby promoting neuronal dysfunction.
authors.affiliation: Department of Physiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
authors.forename: S D
authors.initials: SD
authors.lastname: Yan
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: A M
authors.initials: AM
authors.lastname: Schmidt
authors.forename: J
authors.initials: J
authors.lastname: Brett
authors.forename: G
authors.initials: G
authors.lastname: Godman
authors.forename: Y S
authors.initials: YS
authors.lastname: Zou
authors.forename: C W
authors.initials: CW
authors.lastname: Scott
authors.forename: C
authors.initials: C
authors.lastname: Caputo
authors.forename: T
authors.initials: T
authors.lastname: Frappier
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016875:tau Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D016875:tau Proteins