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AIM Alzheimers disease (AD) is a chronic neurodegenerative disorder and its pathogenesis remains unclear.The present one-drug, one-target paradigm for anti-AD treatment appears to be clinically unsuccessful, and AD arises via multiple pathological or neurotoxic pathways, so the combinational targets composed of several biomolecules based on bio-network may be optimum for the discovery of anti-AD drug.This study aims to search the combinational targets for AD based on traditional Chinese medicine (TCM) with muhi-function, multi-target characteristics using network pharmacology strategy.METHODS The nootropic effects of TCM prescriptions Liu-Wei-Di-huang decoction (LW), Ba-Wei-Di-Huang decoction (BW), Huang-Lian-Jie-Du decoction (HL),Danggui-Shaoyao-San (DSS), Tiaoxin Recipe (TXF), were validated by cognitive behavior test in senescence accelerated mouse prone 8 (SAMP8), and the combinational therapeutic targets were investigated using cDNA microarray, RT-PCR, bioinformatics and computational biology techniques.RESULTS The TCM prescriptions LW, BW, HL, DSS, and TXF significantly improve the cognitive behavior of SAMP8.There are 39 genes expression in hippocampus (H) and 52 genes expression in cerebral cortex (C) regulated by LW in SAMP8, 13 in H and 7 in C by BW, 34 in H and 41 in C by HL, 7 in H and 11 in C by DSS, 24 in H and 11 in C by TXF.These genes regulated by five prescriptions involve in the biomolecular network.There were 384 nodes and 383 edges in the network effected by LW, 384 nodes and 343 edges in the network effected by LW, 86 nodes and 76 edges by BW, 298 nodes and 262 edges by HL, 92 nodes and 85 edges by DSS, 155 nodes and 146 edges by TXF respectively.The hub nodes included 9 molecules, STUB1,STRN4, RPS6KA1, ROCK1, MAP3K3, TICAM2, MAPT, UBE2D2 and PHB.Furthermore, RPS6KA1, SLC17A7 and FHIT are the common nodes effected by every one of five prescriptions and may be therapeutic potential targets for AD.CONCLUSION The molecules including 9 hub nodes and 3 common nodes might formulate the combinational therapeutic target for AD, and is worthy of further studies.