Although in our experiments we did not detect impaired insulin receptor trafficking (Figure 2B and C), and there is also no evidence that ApoE4 carriers are predisposed to the predicted insulin resistance that would be expected to result from intracellular insulin receptor trapping, these data add nevertheless further support to our model which postulates impaired neuronal endosomal vesicle trafficking as the root cause for the increased AD risk imposed by ApoE4 (Chen et al., 2005; Chen et al., 2010; Lane-Donovan and Herz, 2017; Lane-Donovan et al., 2014). Here, INSR is linked to Alzheimer disease.