While these paradoxical results may be partially explained by predominant effects on Abeta clearance, no direct evidence supports this idea; and overexpression of other chaperones, including sHsps, has been shown to be beneficial in animal models of neurodegenerative disease (reviewed in Kourtis and Tavernarakis, 2018; Webster et al., 2019). This evidence concerns the gene APP and neurodegenerative disease.