Among the top genes/proteins dysregulated in Knight-C4, several AD biomarkers including APP, APOE, CLU, SNAP25, GFAP, SNCA, NOTCH3, TARDBP, GRN, MMP9, and C9ORF72 were identified (S3, S8, and S9 Data and Fig 5A and 5D). Here, APOE is linked to Alzheimer disease.