Brain Regional Correspondence Between Alzheimer's Disease Histopathology and Biomarkers of Protein Oxidation

Kenneth Hensley, Nathan Hall, Ramachandran Subramaniam, Pamela Cole, Marni Harris, Michael Aksenov, Marina Aksenova, S. Prasad Gabbita, Jun F. Wu, John M. Carney, Mark Lovell, William R. Markesbery, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

706 Scopus citations

Abstract

Abstract: Four biomarkers of neuronal protein oxidation [W/S ratio of MAL‐6 spin‐labeled synaptosomes, phenylhydrazine‐reactive protein carbonyl content, glutamine synthetase (GS) activity, creatine kinase (CK) activity] in three brain regions [cerebellum, inferior parietal lobule (IPL), and hippocampus (HIP)] of Alzheimer's disease (AD)‐demented and age‐matched control subjects were assessed. These endpoints indicate that AD brain protein may be more oxidized than that of control subjects. The W/S ratios of AD hippocampal and inferior parietal synaptosomes are 30 and 46% lower, respectively, than corresponding values of tissue isolated from control brain; however, the difference between the W/S ratios of AD and control cerebellar synaptosomes is not significant. Protein carbonyl content is increased 42 and 37% in the Alzheimer's HIP and IPL regions, respectively, relative to AD cerebellum, whereas carbonyl content in control HIP and IPL is similar to that of control cerebellum. GS activity decreases an average of 27% in the AD brain; CK activity declines by 80%. The brain regional variation of these oxidation‐sensitive biomarkers corresponds to established histopathological features of AD (senile plaque and neurofibrillary tangle densities) and is paralleled by an increase in immunoreactive microglia. These data indicate that senile plaque‐dense regions of the AD brain may represent environments of elevated oxidative stress.

Original languageEnglish
Pages (from-to)2146-2156
Number of pages11
JournalJournal of Neurochemistry
Volume65
Issue number5
DOIs
StatePublished - Nov 1995

Keywords

  • Alzheimer's disease
  • Amyloid
  • Creatine kinase
  • Electron paramagnetic resonance
  • Free radical
  • Glutamine synthetase
  • Microglia
  • Oxidation
  • Protein carbonyl
  • Spin labeling

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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