Cultured PC12 cells and cortical neurons were also used to analyze the changes in signaling pathways caused by the decreased expression of RFWD2 in vitro and correlations between the expression of related proteins and key signaling pathways of AD at the molecular level.<h4>Results</h4>Decreased RFWD2 expression led to cognitive deficits in AD mice, resulting in mitochondrial swelling, fragmentation of hippocampal neurons, abnormally high reactive oxygen species levels, and an imbalance between antiapoptotic and proapoptotic proteins. This evidence concerns the gene COP1 and Cognitive impairment.