ISG15 and Alzheimer disease: In addition, ICA also found some significant genes of lipoprotein, binding protein, and membrane protein etc. were up-regulated in severe AD (Table 1), such as: GAD2, LDLRAP1, AEBP1, TAP1, UBAP2L, HLA-DRB4, TRHDE, TMEM92, SPARC and SERPINA3; and some significant genes were down-regulated, such as: CABP1, RIMS3, PCSK1, RIMS2, GRIN1, MBP, MOBP, PIP3-E, PLD3, PTPRT, EIF5A, ISG15, RCAN2, RGS4, SRD5A1 (Table 2).