Potentials limitations of mutant APP- and APP/PS-overexpressing mouse models, such as APP/PS1 include, e.g., the lack of non-coding regions of the APP gene that affect splicing of APP mRNA and transcriptional regulation, unphysiological interaction of overexpressed APP and overproduced non Aβ fragments with cellular proteins such as kinesin via JIP-1, non-specific ER impairment upon APP/PS-overexpression, appearance of Aβ entities that are different from those identified in clinical AD brain, different region specificity of Aβ pathology, and inconsistent drug effects [192]. Here, APP is linked to Alzheimer disease.