Preclinical Alzheimer disease: brain oxidative stress, Abeta peptide and proteomics

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 Abeta42, but no significant differences in oligomeric Abeta 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.

Figure 1

Global oxidative stress measurements in control and PCAD IPL. Markers of oxidative and nitrosative damage to proteins were assessed immunochemically. No significant differences were observed between PCAD IPL and control IPL for total protein carbonyls, protein-bound HNE, or 3-nitrotyrosine (n=12 per group).

Figure 2

Representative two-dimensional gel map of proteins that show differential levels in PCAD IPL compared to control IPL. MS-identified spots showing significant alterations in PCAD relative to control are displayed in representative gels with corresponding identities.

Figure 3

Enhanced images of identified proteins with altered levels in PCAD IPL relative to controls, to more clearly show reported changes in spot density.