P3–091: Neuroproteomics in Alzheimer's disease: Expression profiling of the brain proteomes and their relation to proteomes of body fluids

Rapidly progressing proteomics techniques have been widely adopted in most areas of biology and medicine. One of the distinct advantages of proteomic analysis, not attainable with RNA expression data, is the ability to fractionate the cell's proteins into various subpopulations. In neurology and neuroscience, many applications have been entertained in neurotoxicology and neurometabolism, and used in the determination of specific proteomic aspects of individual brain areas and body fluids in neurodegeneration to identify biomarkers. Investigation of brain protein groups in neurodegeneration, such as enzymes, cytoskeleton proteins, chaperones, synaptosomal proteins and antioxidant proteins, is in progress as phenotype related proteomics. The concomitant detection of several hundred proteins on a gel provides sufficiently comprehensive data to determine a pathophysiological protein network and its peripheral representatives. The rapid spread of proteomics technology, which principally consists of two–dimensional gel electrophoresis (2–DE) with in–gel protein digestion of protein spots and identification by mass–spectrometry, has provided an explosive amount of results. In this study, quantitative proteome analysis of AD brains was performed using two–dimensional (2–D) gels. For the higher resolution of 2–DE including the detailed analysis of hydrophobic proteins, we sequentially extracted brain protein. The identified proteins thus examined include enzymes, heat shock proteins and cell structure proteins. We also examined body fluids proteomes to determine the same proteins as in brain proteome using two–dimensional difference gel electrophoresis (2D–DIGE). In neuroscience, ‘neuroproteomics’ (proteomics in the central nervous system) is still in its infancy, with a paucity of studies in the context of the brain. There are several other analytical problems which also need to be overcome, and once solved, will allow for a more comprehensive analysis of the individual disease process.