Blood-based molecular biomarker signatures in Alzheimer's disease: Insights from systems biomedicine perspective

Background: Alzheimers disease (AD) is the progressive neurodegenerative disease characterized by dementia and cognitive dysfunction, and but no peripheral biomarkers available yet that can detect the AD. This study aimed to identify systems biomarkers signatures in the AD through integrative analyses. Method: We used two microarray datasets (GSE4226 and GSE4229) from blood of AD patients to identify differentially expressed genes (DEGs). Geneset and protein overrepresentation analysis, protein-protein interaction (PPI), DEGs-Transcription Factor interactions, DEGs-MicroRNAs interactions, protein-drug interactions, and protein subcellular localizations analyses were performed on common DEGs. Result: Total 25 DEGs were detected between the two datasets. Integration of genome scale transcriptome datasets with biomolecular networks revealed hub proteins (TUBB, ATF3, NOL6, UQCRC1, SND1, CASP2, BTF3, INPP5K, VCAM1, and CSTF1), TFs (FOXC1, ZNF3, GEMIN7, and SMG9), miRNAs (mir-20a-5p, mir-93-5p, mir-16-5p, let-7b-5p, mir-708-5p, mir-24-3p, mir-26b-5p, mir-17-5p, mir-4270, and mir-4441) as already known (BTF3, VCAM, FOXC1, mir-26b-5p, mir-20a-5p, mir-93-5p, let-7b-5p, mir-24-3p) and novel biomarkers candidates in AD. We evaluated the histone modifications of the identified biomolecules (hub genes and TFs). The hub genes and TFs revealed that they possess several histone modification sites associated with AD. The protein-drug interactions revealed 10 candidate drugs consists of antineoplastic (Vinorelbine, Vincristine, Vinblastine, Epothilone D, Epothilone B, CYT997, and ZEN-012), dermatologicals (Podofilox), and immunosuppressive agents (Colchicine). The subcellular localization revealed that interactions of DEGs range from nucleus to plasma membrane through cytosol. Conclusion: This study presents blood based systems molecular biomarker signatures at RNA and protein levels which might be useful as peripheral biomarkers in the AD. The candidate drugs, histone modification sites, and subcellular localizations will be useful in future drug design in the AD.