Alzheimer-specific epitopes of tau represent lipid peroxidation-induced conformations

Quan Liu, Mark A. Smith, Jesus Avilá, John DeBernardis, Mayank Kansal, Atsushi Takeda, Xiongwei Zhu, Akihiko Nunomura, Kazuhiro Honda, Paula I. Moreira, Catarina R. Oliveira, Maria S. Santos, Shun Shimohama, Gjumrakch Aliev, Jack De La Torre, Hossein A. Ghanbari, Sandra L. Siedlak, Peggy L.R. Harris, Lawrence M. Sayre, George Perry

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

Abstract

Several recent studies support a link between τ protein phosphorylation and adduction of τ by reactive carbonyls. Indeed, the phosphorylation- dependent adduction of τ by carbonyl products resulting from lipid peroxidation creates the neurofibrillary tangle-related antigen, Alz50. To determine whether epitopes of carbonyl-modified τ are major conformational changes associated with neurofibrillary tangle formation, we examined seven distinct antibodies raised against neurofibrillary tangles that recognize unique epitopes of τ in Alzheimer disease. Consistently, all seven antibodies recognize τ more strongly (4- to 34-fold) after treatment of normal τ with the reactive carbonyl, 4-hydroxy-2-nonenal (HNE), but only when τ 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 τ promote and contribute to the generation of the major conformational properties defining neurofibrillary tangles.

Original languageEnglish
Pages (from-to)746-754
Number of pages9
JournalFree Radical Biology and Medicine
Volume38
Issue number6
DOIs
Publication statusPublished - 2005 Mar 15

Keywords

  • 4-Hydroxy-2-nonenal
  • Alzheimer disease
  • Free radicals
  • Immunocytochemistry
  • Lipid peroxidation
  • Paired helical filament
  • τ modification

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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