title: Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations.
abstract: Several recent studies support a link between tau protein phosphorylation and adduction of tau by reactive carbonyls. Indeed, the phosphorylation-dependent adduction of tau by carbonyl products resulting from lipid peroxidation creates the neurofibrillary tangle-related antigen, Alz50. To determine whether epitopes of carbonyl-modified tau are major conformational changes associated with neurofibrillary tangle formation, we examined seven distinct antibodies raised against neurofibrillary tangles that recognize unique epitopes of tau in Alzheimer disease. Consistently, all seven antibodies recognize tau more strongly (4- to 34-fold) after treatment of normal tau with the reactive carbonyl, 4-hydroxy-2-nonenal (HNE), but only when tau is in the phosphorylated state. These findings not only support the idea that oxidative stress is involved in neurofibrillary tangle formation occurring in brains of Alzheimer disease patients, but also show, for the first time, that HNE modifications of tau promote and contribute to the generation of the major conformational properties defining neurofibrillary tangles.
authors.affiliation: Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Jesus
authors.initials: J
authors.lastname: Avilá
authors.forename: John
authors.initials: J
authors.lastname: DeBernardis
authors.forename: Mayank
authors.initials: M
authors.lastname: Kansal
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Honda
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
authors.forename: Jack
authors.initials: J
authors.lastname: de la Torre
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghanbari
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Siedlak
authors.forename: Peggy L R
authors.initials: PL
authors.lastname: Harris
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Sayre
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000737:chemistry; D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D051379:Mice; D008957:Models, Genetic; D018384:Oxidative Stress; D010766:Phosphorylation; D011487:Protein Conformation; D013997:Time Factors; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D000939:Epitopes; D016875:tau Proteins; C027576:4-hydroxy-2-nonenal