Given the unreported role of FBXL16 in the ubiquitination of APP in both lentiviral FBXL16-overexpressing and FBXL16-conditional knockout (cko) mice, proteomics and bioinformatics analyses were adopted to evaluate the neuroprotective role of FBXL16 in the degradation of APP, cognitive ability and neuroinflammation in AD mouse models, which has provided scientific evidence for the future development of AD therapy. The gene discussed is FBXL16; the disease is Alzheimer disease.