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The article discusses research by J. Lamb et al. that seeks to create a collection of gene-expression profiles of human cells. The repository is a step towards creating a data-base of gene-expression of human diseases, which could dramatically shorten the time it takes to develop treatments for disease. Lamb's "connectivity map" shows the signatures of 164 small molecules, which include those of drugs and diseases including Alzheimer's. The database is accessible through the Internet. The map can help researchers identify how molecules interact with one another to prevent genetic diseases.

Abstract: Apolipoprotein E4 (APOE4) allele is a major risk factor for late-onset familial and sporadic Alzheimer disease (AD). The mechanism of action of APOE in the etiology of AD remains unclear. Using gene expression (microarray) analysis of human hippocampus from APOE3/3 AD and APOE4/4 AD cases, we found different gene transcription patterns between APOE4/4 and APOE3/3 AD cases. The expression of APOE4/4 alleles, in comparison to APOE3/3, is associated with upregulation of multiple gene transcripts encoding cell growth suppresser or arrest, signal transduction, myelinogenesis, cell adhesion and migration, heavy metal metabolism and detoxification. Whereas the APOE4 gene expression is associated with downregulation of gene transcripts involved in mitochondrial oxidative phosphorylation and energy metabolism, synaptic vesicle docking and fusing, and synaptic plasticity compared to APOE3. These mechanisms may contribute increased risk for AD and for cognitive dysfunction in AD patients who carry the APOE4 allele(s). [Copyright &y& Elsevier]