To elicit lysosomal enhancement in mouse models of AD, we administered Z-Phe-Ala-diazomethylketone (PADK), a weak inhibitor of cathepsin B and L (cathepsin B IC50 = 9.4±2.4 μM) as well as a lysosomal modulator previously shown to cause a feedback response involving marked up-regulation of cathepsin isoform expression in vitro[19]–[21]. This evidence concerns the gene CTSS and Alzheimer disease.