This mouse bears a partial trisomy of a segment of Mmu16, containing Leupeptin hemisulfate approximately 92 genes orthologous to Hsa21 genes ; in addition, the Ts65Dn mouse also carries a trisomy of,10 Mb of Mmu17 containing 60 genes that are not homologous to Hsa21. Thus, the set of genes that are not triplicated in DS that are trisomic in this model may also modulate or modify different phenotypes in a manner that differs from that found in single transgenic mice or other segmental trisomic mice. Several studies have implicated Dyrk1A overexpression in the cognitive phenotype detected in animals carrying extra copies of this gene or in segmental trisomic mice, which also overexpress the Dyrk1A gene. A recent study revealed that normalization of the Dyrk1A expression level exclusively in the hippocampus by injecting a viral vector containing inhibitory Dyrk1A shRNA did not improve the learning abilities of TS mice; however, this intervention enhanced their search strategy during the MWM test. The discrepancy between these results and the partial rescue of the performance on the MWM test found in the present study may be explained by the tissues in which Dyrk1A expression was normalized in each study. The reference and working memory components and the longterm consolidation process in the spatial learning component of the MWM test are dependent on the integrity of not only the hippocampus but also the prefrontal cortex, which is a structure that is also affected in DS. In this study, the Dyrk1A gene dosage was also normalized in the cortex and, presumably, in all tissues in which Dyrk1A is overexpressed. Therefore, Dyrk1A normalization may result in more efficient learning. Additional support for the role of Dyrk1A in the altered cognitive abilities found in DS mouse models comes from studies demonstrating that the pharmacological inhibition of this gene using epigallocatechin gallate, improves hippocampaldependent learning and thigmotaxis in TgDyrk1A and Ts65Dn mice.In addition, in a pilot clinical trial of individuals with DS, administration of EGCG enhanced their accuracy in visual memory Sulfadoxine recognition and spatial working memory, suggesting a positive effect of this compound on the prefrontal system.