Indeed, the penetrance and expressivity of disease phenotypes, including AD-like pathology, vary between DS individuals, and this has been attributed to the presence of modifier alleles on Hsa21 (e.g., DYRK1A, BACE2, miR-155) or other chromosomes, such as APOE (Sherman et al., 2007). This evidence concerns the gene BACE2 and Dravet syndrome.