To identify how SIRT2 regulated BACE1 in AD progress, we performed co‐immunoprecipitation (Co‐IP) in the SIRT2‐overexpressing SY5Y cell line and conducted mass spectrometry (MS) analysis of the SIRT2 trapped proteins to screening the potential substrate of SIRT2 in the neural cell line. This evidence concerns the gene BACE1 and Alzheimer disease.