RESUMEN
Multiple gene expression alterations have been linked to Alzheimer's disease (AD), implicating multiple metabolic pathways in its pathogenesis. However, a clear distinction between AD-specific gene expression changes and those resulting from nonspecific responses to toxic aggregating proteins has not been made. We investigated alterations in gene expression induced by human beta-amyloid peptide (Aß) in a Caenorhabditis elegans AD model. Aß-induced gene expression alterations were compared with those caused by a synthetic aggregating protein to identify Aß-specific effects. Both Aß-specific and nonspecific alterations were observed. Among Aß-specific genes were those involved in aging, proteasome function, and mitochondrial function. An intriguing observation was the significant overlap between gene expression changes induced by Aß and those induced by Cry5B, a bacterial pore-forming toxin. This led us to hypothesize that Aß exerts its toxic effect, at least in part, by causing damage to biological membranes. We provide in vivo evidence consistent with this hypothesis. This study distinguishes between Aß-specific and nonspecific mechanisms and provides potential targets for therapeutics discovery.