In our study, we found that the expression of CPLX2 was significantly decreased in 3xTg-AD mice compared with the WT mice and modulated by the treatment of Rg1, suggesting an involvement of CPLX2 in behavioral impairment of 3xTg-AD mice and the protective effects of Rg1 on memory and depression. Here, CPLX2 is linked to Alzheimer disease.