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

Gene expression in the Alzheimer brain and normal brain was compared by molecular indexing, an advanced version of differential display. Using this technique, each gene was represented by a 3'-end cDNA fragment generated by class IIS restriction enzymes. The fragments were divided into 384 groups, and each group was separated by denaturing polyacrylamide gel electrophoresis. Comparison of gel patterns revealed 70 genes exhibiting marked differences in gene expression between AD and normal brain. A similarity search revealed 22 genes already reported, including those considered to be related to the pathogenesis such as G protein, G protein-related, and mitochondrial components. Detailed analysis of one from those only matched to EST sequences 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 potentially powerful approach to listing genes related to the pathogenesis.