A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans. In this article, we report that supplementation of this cranberry extract delayed A beta toxicity-triggered body paralysis in the C. elegans AD model. Genetic analyses indicated that the cranberry-mediated A beta toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C. elegans against A beta toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated A beta toxicity in C. elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view.