Elevated levels of 3-nitrotyrosine in brain from subjects with amnestic mild cognitive impairment: Implications for the role of nitration in the progression of Alzheimer's disease

D. Allan Butterfield, Tanea T. Reed, Marzia Perluigi, Carlo De Marco, Raffaella Coccia, Jeffrey N. Keller, William R. Markesbery, Rukhsana Sultana

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

Abstract

A number of studies reported that oxidative and nitrosative damage may be important in the pathogenesis of Alzheimer's disease (AD). However, whether oxidative damage precedes, contributes directly, or is secondary to AD pathogenesis is not known. Amnestic mild cognitive impairment (MCI) is a clinical condition that is a transition between normal aging and dementia and AD, characterized by a memory deficit without loss of general cognitive and functional abilities. Analysis of nitrosative stress in MCI could be important to determine whether nitrosative damage directly contributes to AD. In the present study, we measured the level of total protein nitration to determine if excess protein nitration occurs in brain samples from subjects with MCI compared to that in healthy controls. We demonstrated using slot blot that protein nitration is higher in the inferior parietal lobule (IPL) and hippocampus in MCI compared to those regions from control subjects. Immunohistochemistry analysis of hippocampus confirmed this result. These findings suggest that nitrosative damage occurs early in the course of MCI, and that protein nitration may be important for conversion of MCI to AD.

Original languageEnglish
Pages (from-to)243-248
Number of pages6
JournalBrain Research
Volume1148
Issue number1
DOIs
StatePublished - May 7 2007

Bibliographical note

Funding Information:
The authors thank the University of Kentucky ADC Clinical and Neuropathology Cores for providing the brain specimens used for this study. This work was supported in part by grants from NIH to D.A.B. [AG-05119; AG-10836] and to W.R.M [AG-05119, AG-05144]. W.R.M. also thanks the Abercrombie Foundation for financial support.

Keywords

  • Alzheimer's disease
  • Hippocampus
  • Inferior parietal lobule
  • Mild cognitive impairment
  • Nitrosative stress
  • Protein nitration

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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