Indoleamine 2,3-dioxygenase and 3-hydroxykynurenine modifications are found in the neuropathology of Alzheimer's disease

David J. Bonda, Maneesh Mailankot, Jeremy G. Stone, Matthew R. Garrett, Magdalena Staniszewska, Rudy J. Castellani, Sandra L. Siedlak, Xiongwei Zhu, Hyoung Gon Lee, George Perry, Ram H. Nagaraj, Mark A. Smith

Research output: Contribution to journalArticlepeer-review

106 Scopus citations

Abstract

Tryptophan metabolism, through the kynurenine pathway, produces neurotoxic intermediates that are implicated in the pathogenesis of Alzheimer's disease. In particular, oxidative stress via 3-hydroxykynurenine (3-HK) and its cleaved product 3-hydroxyanthranilic acid (3-HAA) significantly damages neuronal tissue and may potentially contribute to a cycle of neurodegeneration through consequent amyloid-β accumulation, glial activation, and up-regulation of the kynurenine pathway. To determine the role of the kynurenine pathway in eliciting and continuing oxidative stress within Alzheimer's diseased brains, we used immunocytochemical methods to show elevated levels of 3-HK modifications and the upstream, rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO-1) in Alzheimer's diseased brains when compared to controls. Importantly, the association of IDO-1 with senile plaques was confirmed and, for the first time, IDO-1 was shown to be specifically localized in conjunction with neurofibrillary tangles. As senile plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease, our study provides further evidence that the kynurenine pathway is involved with the destructive neurodegenerative pathway of Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)161-168
Number of pages8
JournalRedox Report
Volume15
Issue number4
DOIs
StatePublished - Aug 1 2010

Keywords

  • Alzheimer's disease
  • amyloid-ß
  • hyperphosphorylated tau
  • indoleamine 2,3-dioxygenase
  • kynurenine
  • kynurenine pathway
  • quinolinic acid
  • tryptophan

ASJC Scopus subject areas

  • Biochemistry, medical
  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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