Disease State, Age, Sex, and Post-Mortem Time-Dependent Expression of Proteins in AD vs. Control Frontal Cortex Brain Samples

T.      Muller; K.      Jung; A.      Ullrich; A.      Schrotter; H.   E.   Meyer; C.      Stephan; R.      Egensperger; K.      Marcus

Abstract

Human post-mortem brain samples are excellent source material for the analysis of age-related disorders such as Alzheimers disease (AD). Moreover, data obtained from cell culture- or mouse model-related experiments often need to be validated by using human tissue. In a variety of studies over the last few years, a huge list of genes or proteins with differential expression or abundance between AD-related and control tissue has been reported. However, highly important issues such as changes in post-mortem time, sex, age etc. of the patients have been rarely included in the analysis. In our study we examined human frontal brain samples of 10 AD patients vs. 10 unaffected controls using state-of-the-art two dimensional DIGE proteomics in order to analyze protein expression of up to 10,000 proteins in parallel. Data were analyzed using well established DIGE-software tool as well as an analysis of covariance model including the factor effects of group and sex and the covariable effects of age and post-mortem time. Within this study we report protein expression changes in AD vs. control human frontal brain samples without any influence of other parameters as well as expression changes depending on the parameters mentioned above. In fact, some proteins previously suggested a state of being dysregulated in AD vs. controls revealed age or sex-dependent regulation. Our analysis suggests the necessity of integrating additionally available covariables in comparative proteome studies of two different sets of human tissue.

Keywords: post-mortem, brain samples, Alzheimer's disease (AD), cell culture, proteomics, age, sex, human tissue