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

Article type: Research Article

Authors: Aluise, Christopher D.^{a; b; c} | Robinson, Renã A.S.^{a; b; c} | Cai, Jian^d | Pierce, William M.^d | Markesbery, William R.^{c; †} | Butterfield, D. Allan^{a; b; c; *}

Affiliations: [a] Department of Chemistry, University of Kentucky, Lexington, KY, USA | [b] Center of Membrane Sciences, University of Kentucky, Lexington, KY, USA | [c] Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA | [d] Department of Pharmacology, University of Louisville, Louisville, KY, USA

Correspondence: [*] Correspondence to: Prof. D. Allan Butterfield, Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA. Tel.: +1 859 257 3184; Fax: +1 859 257 5876; E-mail: [email protected].

Note: [†] Deceased Jan. 30, 2010.

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.

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

DOI: 10.3233/JAD-2010-101083

Journal: Journal of Alzheimer's Disease, vol. 23, no. 2, pp. 257-269, 2011