BACE1 and Alzheimer disease: Since in AD, enhanced amyloidogenic processing of APP by BACE1 involves the dysfunction of retromer complex and, thus, sequestration of BACE1 and its substrate APP in early endosomal compartments [49,50], where acidic pH enables optimal cleavage by BACE1, we hypothesized that dysfunctional retromer transport causes enhanced BACE1-mediated proteolysis in NPC as well.