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The increasing number of applications of silver nanoparticles (AgNP) prompted us to assess their toxicityin vivo. We have investigated their effects on wild type and transgenicCaenorhabditis elegans(C. elegans) strains expressing two prototypic amyloidogenic proteins: β2-microglobulin and Aβ peptide3–42. The use ofC. elegansallowed us to highlight AgNP toxicity in the early phase of the worm’s life cycle (LC50survival, 0.9 µg/ml). A comparative analysis of LC50values revealed that our nematode strains were more sensitive to assess AgNP toxicity than the cell lines, classically used in toxicity tests. Movement and superoxide production in the adult population were significantly affected by exposure to AgNP; the transgenic strains were more affected than the wild type worms. Our screening approach could be applied to other types of nanomaterials that can enter the body and express any nanostructure-related bioactivities. We propose thatC. elegansreproducing the molecular events associated with protein misfolding diseases, e.g. Alzheimer’s disease and systemic amyloidosis, may help to investigate the specific toxicity of a range of potentially harmful molecules. Our study suggests that transgenicC. elegansmay be used to predict the effect of chemicals in a “fragile population”, where an underlying pathologic state may amplify their toxicity. [ABSTRACT FROM AUTHOR]