Redox proteomics analysis of brains from subjects with amnestic mild cognitive impairment compared to brains from subjects with preclinical alzheimer's disease: Insights into memory loss in MCI

Christopher D. Aluise, Ren A.S. Robinson, Jian Cai, William M. Pierce, William R. Markesbery, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Alzheimer's disease (AD) is a central nervous system disorder pathologically characterized by senile plaques, neurofibrillary tangles, and synapse loss. A small percentage of individuals with normal antemortem psychometric scores, after adjustments for age and education, meet the neuropathological criteria for amnestic mild cognitive impairment (MCI) or AD; these individuals have been termed 'preclinical' or 'asymptomatic' AD (PCAD). In this study, we employed the immunochemical slot-blot method and two-dimensional gel-based redox proteomics to observe differences in protein levels and oxidative modifications between groups with equal levels of AD pathology who differ in regards to clinical symptoms of memory impairment. Results of global oxidative stress measurements revealed significantly higher levels of protein carbonyls in the MCI inferior parietal lobule (IPL) relative to PCAD (and controls), despite equal levels of neuropathology. Proteomics analysis of the IPL revealed differences in protein levels and specific carbonylation that are consistent with preservation of memory in PCAD and apparent memory decline in MCI. Our data suggest that marked changes occur at the protein level in MCI that may cause or reflect memory loss and other AD symptoms.

Original languageEnglish
Pages (from-to)257-269
Number of pages13
JournalJournal of Alzheimer's Disease
Volume23
Issue number2
DOIs
StatePublished - 2011

Keywords

  • Alzheimer's disease
  • brain
  • mild cognitive impairment
  • oxidative stress
  • preclinical Alzheimer's
  • proteomics
  • redox proteomics
  • two dimensional gel electrophoresis

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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