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 non-specific responses to toxic aggregating proteins has not been made. We investigated alterations in gene expression induced by human β-amyloid peptide (Aβ) in a Caenorhabditis elegans Alzheimer’s disease model. Aβ-induced gene expression alterations were compared to those caused by a synthetic aggregating protein to identify Aβ-specific effects. Both Aβ-specific and non-specific alterations were observed. Among Aβ-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 Aβ and those induced by Cry5B, a bacterial pore-forming toxin. This led us to hypothesize that Aβ 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 Aβ-specific and non-specific mechanisms and provides potential targets for therapeutics discovery.