Analysis of brain proteins in Alzheimer's disease using high-resolution two-dimensional gel electrophoresis

Two-dimensional gel electrophoresis (2-DE), a method which can be used to a nalyze the expression of many proteins, is a promising and powerful approac h which we have begun to use in the characterization of the complex patholo gic processes in Alzheimer's disease (AD). In the present study, a reliable 2-DE database of human brain proteins was created by improving the reprodu cibility of 2-DE images using an immobilized pH gradient (IPG) for the firs t dimension gel electrophoresis and Melanie II as the program for data anal ysis. The brain samples were taken from the temporal cortex of brains at au topsy from 15 AD patients and 15 age-matched controls with non-neurological disorders. About 700 spots were located as consistently expressed proteins in the human brain, all of which were expressed also in AD brains. Compari ng the density of spots between AD and normal control, we found that five p rotein spots were significantly increased, 28 spots were significantly decr eased and nine spots were detected only in AD. Two spots among those signif icantly increased and one spot among those significantly decreased were ide ntified as glial fibrillary acidic proteins. The database of brain proteins in AD constructed for the present study, including the statistical data of density changes in AD, should be a useful beginning for a comprehensive hu man 2-DE database available via the Internet, which will facilitate further investigation of pathogenic protein alterations in AD. (C) 1999 Elsevier S cience B.V. All rights reserved.