CTSB and Alzheimer disease: However, recent studies in Drosophila models of AD expressing full-length amyloid precursor proteins (APPs) or the C-terminal fragment of APP (APP.C99), or in human induced pluripotent stem cell (iPSC)-derived neuronal models of AD, showed that RET was activated, as demonstrated by the increased production of RET-ROS and decreased NAD+/NADH ratio [47].