Analysis of the proteomic profiling of brain tissue in Alzheimer's disease.
In proteome analysis, it is necessary to separate proteins as a first step prior to characterization. Thus, the overall performance of the analysis depends strongly on the separation tool, which is usually two-dimensional electrophoresis (2DE). We have utilized 2DE to begin characterization of the complex pathologic processes in Alzheimer's disease (AD). In the present study, we show how a reliable 2-DE database of brain proteins in Alzheimer's disease was created, improving reproducibility by using an immobilized pH gradient (IPG) for the first dimension gel electrophoresis. The recent progress in this field, and future prospects in this area are also discussed. Preparation of brain proteins into a suitable solubilized state enabled us to separate over 1000 well-defined protein spots in each 2-DE. A comparison of the density of the spots identified on the reference map between the AD and control group, showed that 5 protein spots were significantly increased, 28 spots were significantly decreased and 7 spots were specifically detected in AD. Two spots among those significantly increased and one spot among those significantly decreased were identified as GFAP related. It is hoped that comparative studies to identify, quantitate, and characterize the proteins differentially expressed in normal brain versus diseased brain will give insight into the mechanisms of pathogenesis and allow the development of a strategy to control both the etiology and course of the diseases.
Tsuji
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T
Department of Neurology, Faculty of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606, Japan.
Shimohama
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D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002102:Cadaver; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009417:Nerve Tissue / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D012016:Reference Values
D008565:Membrane Proteins; D020543:Proteome