Such mouse models, however, often suffer from experimental limitations caused by overproduction of APP fragments such as C-terminal fragment of APP generated by β-secretase (β-CTF) and APP intracellular domain (AICD), both of which do not appear to accumulate in AD brains and may induce artificial endosomal abnormalities (4) and transcriptional malfunctions (5), respectively. This evidence concerns the gene APP and Alzheimer disease.