# Transcriptional Profiling of Hippocampus Identifies Network Alterations in Alzheimer's Disease
## 3 Results
### Protein-Protein Interactions  
We further explored the protein-protein interactions of 76 consensus DEGs using STRING and the network found was visualized with Cytoscape (Figure 6). We obtained a network of 39 nodes and 81 edges. \begin{table}
\begin{tabular}{l l} \hline \hline
**Down-Regulated Genes** & **Drugs** \\ \hline
**CA10** & (1) ZONISAAMIDE \\ \hline
**CACNG2** & (1) GABAPENTIN \\ \hline  & (1) APOMORPHINE \\
**CALY** & (2) CLOZAPIINE \\  & (3) TRIFLUOPERAZINE \\ \hline
**CKMT1A** & (1) CREATING \\ \hline
**GAD1** & (1) GLUTAMIC ACID \\ \hline
**GLS2** & (1) GLUTAMIC ACID \\ \hline  & (1) ASPARTIC ACID \\
**GOT1** & (2) CYSTEINE \\  & (3) GLUTAMIC ACID \\ \hline
**MAP4** & (1) DOCETAXEL \\  & (2) PACLITAXEL \\ \hline  & (1) CRIZOTINIB \\  & (2) ERLOTINIB \\  & (3) CABOZANTINIB \\  & (4) GEEITINIB \\  & (5) PAZOPANIB \\  & (6) AFATINIB \\  & (7) ALECITINIB \\  & (8) ALTIRATINIB \\  & (9) AMG-208 \\  & (10) AMG-337 \\  & (11) AMUVATINIB \\
**MET** & (12) BMS-777607 \\  & (13) BMS-817378 \\  & (14) FOREITINB \\  & (15) GOLVATINIB \\  & (16) JINJ-8877605 \\  & (17) MGCD-265 \\  & (18) MK-2461 \\  & (19) MK-8033 \\  & (20) PF-04217903 \\  & (21) PHA-665752 \\  & (22) SAVOLITINIB \\  & (23) TIVANTINIB \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Down-regulated genes and their interactions with known drugs in at least two of three drug databases (DGIdb, DrugCentral, and The Drug Repurposing Hub). \begin{table}
\begin{tabular}{l l} \hline \hline
**Up-Regulated Genes** & **Drugs** \\ \hline  & (1) OPICAPONE \\  & (2) TOLCAPONE \\
**COMT** & (3) ENTACAPONE \\  & (4) NIALAMIDE \\  & (5) 2-METHOXYESTRADIOL \\ \hline
**PRKG1** & (1) GSK-690693 \\ \hline  & (1) RUPATADINE \\
**PTAFR** & (2) APAFANT \\  & (3) FOROPFAANT \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Up-regulated genes and their interactions with known drugs in at least two of three drug databases (DGIdb, DrugCentral, and The Drug Repurposing Hub). Figure 4: Co-expression network obtained with weighted correlation network analysis (WGCNA) and visualized with Cytoscape. Dark blue nodes correspond to the genes with a higher degree centrality. Grey colored edges indicate the gene interactions. Figure 3: Hierarchical cluster dendrogram and gene module identified by weighted correlation network analysis (WGCNA). Gray genes are not included in any module. The MCODE plugin of Cytoscape was used to identify interconnected regions of the network identified with STRING and we obtained a cluster of 12 genes (AMPH, CA10, CALY, NEFL, SNAP25, SNAP91, SNCB, STMN2, SV2B, SYN2, SYT1, and SYT13) and 42 edges (Figure 7). Figure 5: Pathway analysis using ClueGo from 64 genes obtained with WGCNA. Nodes represent GO terms and the node size represents the term’s enrichment significance. **(A)** Clathrin coat assembly and synaptic vesicle endocytosis; **(B)** DNA damage response signal transduction by p53 class mediator; **(C)** positive regulation of transforming growth factor beta receptor signaling pathway and glutamine family amino acid catabolic process; **(D)** neurofilament cytoskeleton organization and neural nucleus development. The 64 genes of the module obtained with WCGNA and the 12 genes present in the cluster found with MCODE have in common 11 genes (AMPH, CA10, CALY, NEFL, SNAP25, SNAP91, SNCB, STMN2, SV2B, SYN2, and SYT1). We also verified whether the 64 genes present in the module obtained with WCGNA are also targets of known drugs and found that the AD down-regulated genes CA10, CACNG2, CALY, GAD1, GLS2, GOT1, MAP4, and MET interact with known drugs. GOT1 and GAD1 are also genes with a higher degree centrality. We also found that 2 out of 12 genes present in the MCODE cluster are also targets of known drugs (CA10 and CALY). All three upregulated genes (COMT, PRKG1, and PTAFR) that are targets of known drugs are present in the WCGNA module. No up-regulated gene present in the MCODE cluster is a target of known drugs. Figure 6: Protein–protein interactions of 76 consensus differentially expressed genes in [PERSON]’s disease.