Amyloid β Induces Hormetic-Like Effects Through Major Stress Pathways in a C. elegans Model of Alzheimer's Disease

Abstract

Amyloid {beta} (A{beta}) is a peptide known for its characteristic aggregates in Alzheimers Disease and its ability to induce a wide range of detrimental effects in various model systems. However, A{beta} has also been shown to induce some beneficial effects, such as antimicrobial properties against pathogens. In this work, we explore the influence of A{beta} in stress resistance in a C. elegans model of Alzheimers Disease. We found that C. elegans that express human A{beta} exhibit increased resistance to heat and hypoxia, but not to oxidative stress. This beneficial effect of A{beta} was driven from A{beta} in neurons but not muscles, and the abundance of A{beta} in neurons correlated with stress resistance levels. Transcriptomic analysis revealed that this selective stress resistance was mediated by the Heat Shock Protein (HSPs) family of genes. Furthermore, neuropeptide signaling was necessary for A{beta} to induce stress resistance, suggesting neuroendocrine signaling plays a major role in activating organismal stress response pathways. These results highlight the potential beneficial role of A{beta} in cellular function, as well as its complex effects on cellular and organismal physiology that must be considered when using C. elegans as a model for Alzheimers Disease.