Buildingupon our established ApoE4-expressing H4 neuroglioma cells, the currentwork aims to explore the capability of OrbiSIMS as a screening toolfor identifying alterations in lipids, metabolites, and peptide fragmentsinfluenced by the AD risk gene ApoE4 in H4 cells followed by LC-MS/MSvalidation to confirm the reliability of OrbiSIMS as a screening toolfor metabolomic studies. This evidence concerns the gene APOE and Alzheimer disease.