In summary, our study revealed that APN deficiency could induce circadian rhythm disorder and showed that APN might improve the abnormal expression of Bmal1 mRNA/protein induced by Aβ31‐35 in HT22 hippocampal neurons by inhibiting the activity of GSK3β, which provides a novel approach for the treatment of AD. The gene discussed is GSK3B; the disease is Alzheimer disease.