Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease

M. A. Bradley, W. R. Markesbery, M. A. Lovell

Research output: Contribution to journalArticlepeer-review

165 Scopus citations

Abstract

Previous studies demonstrate increased levels of 4-hydroxynonenal (HNE) and acrolein in vulnerable brain regions of subjects with mild cognitive impairment and late-stage Alzheimer disease (LAD). Recently preclinical AD (PCAD) subjects, who demonstrate normal antemortem neuropsychological test scores but abundant AD pathology at autopsy, have become the focus of increased study. Levels of extractable HNE and acrolein were quantified by gas chromatography-mass spectrometry with negative chemical ionization, and protein-bound HNE and acrolein were quantified by dot-blot immunohistochemistry in the hippocampus/parahippocampal gyrus (HPG), superior and middle temporal gyri (SMTG), and cerebellum (CER) of 10 PCAD and 10 age-matched normal control (NC) subjects. Results of the analyses show a significant (P<0.05) increase in levels of extractable acrolein in the HPG of PCAD subjects compared to age-matched NC subjects and a significant decrease in extractable acrolein in PCAD CER. Significant increases in protein-bound HNE in HPG and a significant decrease in CER of PCAD subjects compared to NC subjects were observed. No significant alterations were observed in either extractable or protein-bound HNE or acrolein in the SMTG of PCAD subjects. Additionally, no significant differences in levels of protein carbonyls were observed in the HPG, SMTG, or CER of PCAD subjects compared to NC subjects.

Original languageEnglish
Pages (from-to)1570-1576
Number of pages7
JournalFree Radical Biology and Medicine
Volume48
Issue number12
DOIs
StatePublished - Jun 2010

Bibliographical note

Funding Information:
This research was supported by NIH Grants 5P01-AG05119 and P30-AG028383 . The authors thank Ms. Sonya Anderson for subject demographic data and Ms. Paula Thomason for editorial assistance.

Keywords

  • Free radicals
  • Lipid peroxidation
  • Oxidative damage
  • Preclinical Alzheimer disease

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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