The top significant differentially expressed genes in APOE4 carriers with the highest direct association scores generated from the DISQOVER platform were NRGN, IGF2, GMPR, CLDN5, and SMIM24. NRGN has been thoroughly studied as a potential AD biomarker in blood and cerebrospinal fluid [70, 71]. The gene discussed is CLDN5; the disease is Alzheimer disease.