Our laboratories and collaborators have focused on the apparently Aβ-independent endosomal pathway changes that are seen in Down syndrome (DS) (Cataldo et al., 2000, 2003, 2008) and as a result of the expression of the apolipoprotein E ε4 allele (ApoE4) (Nuriel et al., 2017). Here, APOE is linked to Dravet syndrome.