The beta-amyloid peptide, the major component of the senile plaques in Alzheimer's disease (AD), has been probed to be toxic to neurons both in vivo and in vitro. Several mechanisms have been proposed to be involved in the amyloid-induced neurotoxicity; among others it has been suggested that the beta-amyloid peptide exerts its toxic effect mainly by activating the surrounding microglia population, which in turn induces the synthesis and release of preapoptotic and pro-inflammatory factors. In addition, a direct effect of beta-amyloid on neurons has been also described. However, the precise mechanisms involved in the amyloid-induced neurotoxicity have been not yet definitely clarified. To characterize the effects directly induced on neurons, we have analyzed the gene expression profile induced by the 25-35 beta-amyloid fragment in human SH-SY5Y neuroblastoma cells, by using the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Our results confirm that beta-amyloid may directly induce neuronal cell death; activating signals that in vivo have been described as causative of Alzheimer's disease.