Preclinical Alzheimer disease: Brain oxidative stress, Aβ peptide and proteomics

Christopher D. Aluise, Renã A.Sowell Robinson, Tina L. Beckett, M. Paul Murphy, Jian Cai, William M. Pierce, William R. Markesbery, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Alzheimer disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory loss and subsequent dementia and neuropathologically by senile plaques, neurofibrillary tangles, and synapse loss. Interestingly, a small percentage of individuals with normal antemortem psychometric scores meet the neuropathological criteria for AD (termed 'preclinical' AD (PCAD)). In this study, inferior parietal lobule (IPL) from PCAD and control subjects was compared for oxidative stress markers by immunochemistry, amyloid beta peptide by ELISA, and identification of protein expression differences by proteomics. We observed a significant increase in highly insoluble monomeric Aβ42, but no significant differences in oligomeric Aβ nor in oxidative stress measurements between controls and PCAD subjects. Expression proteomics identified proteins whose trends in PCAD are indicative of cellular protection, possibly correlating with previous studies showing no cell loss in PCAD. Our analyses may reveal processes involved in a period of protection from neurodegeneration that mimic the clinical phenotype of PCAD.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalNeurobiology of Disease
Volume39
Issue number2
DOIs
StatePublished - Aug 2010

Bibliographical note

Funding Information:
This work was supported in part by NIH grants to DAB [ AG-05119 ]. We are grateful to the Clinical and Neuropathology Cores of the University of Kentucky Alzheimer's Disease Clinical Center for providing well characterized tissue samples from volunteers in the longitudinal normal aging study.

Keywords

  • Amyloid beta
  • Brain
  • Inferior parietal lobule (IPL)
  • Oxidative stress
  • Preclinical Alzheimer
  • Proteomics

ASJC Scopus subject areas

  • Neurology

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