Gene expression profile in Alzheimer's brain screened by molecular indexing

Gene expression in the Alzheimer brain and normal brain was compared by mol ecular indexing, an advanced version of differential display. Using this te chnique, each gene was represented by a 3'-end cDNA fragment generated by c lass IIS restriction enzymes. The fragments were divided into 384 groups, a nd each group was separated by denaturing polyacrylamide gel electrophoresi s. Comparison of gel patterns revealed 70 genes exhibiting marked differenc es in gene expression between AD and normal brain. A similarity search reve aled 22 genes already reported, including those considered to be related to the pathogenesis such as G protein, G protein-related, and mitochondrial c omponents. Detailed analysis of one from those only matched to EST sequence s revealed a novel protein with leucine-zipper and SH3-binding motifs. Its expression was suppressed in a subpopulation of cortical pyramidal neurons in the AD brain, suggesting a possible relation to the pathogenesis. Thus, genome-scale analysis of gene expression of neurodegeneration is a potentia lly powerful approach to listing genes related to the pathogenesis. (C) 200 1 Elsevier Science B.V. All rights reserved.