In APP/PS1dE9 mice, there is an alteration of rhythmic expression patterns of BACE 1 and ApoE in the hippocampus, which is activated by E4BP4 and BMAL1, respectively. So, finally, study suggests that hippocampal clock and circadian oscillation of AD risk gene are regulated by orexin signaling. This evidence concerns the gene CLOCK and Alzheimer disease.