Molecular crosstalk between COVID-19 and Alzheimer's disease using microarray and RNA-seq datasets: A system biology approach.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The clinical and epidemiological analysis reported the association between SARS-CoV-2 and neurological diseases. Among neurological diseases, Alzheimer's disease (AD) has developed as a crucial comorbidity of SARS-CoV-2. This study aimed to understand the common transcriptional signatures between SARS-CoV-2 and AD. MATERIALS AND METHODS: System biology approaches were used to compare the datasets of AD and COVID-19 to identify the genetic association. For this, we have integrated three human whole transcriptomic datasets for COVID-19 and five microarray datasets for AD. We have identified differentially expressed genes for all the datasets and constructed a protein-protein interaction (PPI) network. Hub genes were identified from the PPI network, and hub genes-associated regulatory molecules (transcription factors and miRNAs) were identified for further validation. RESULTS: A total of 9,500 differentially expressed genes (DEGs) were identified for AD and 7,000 DEGs for COVID-19. Gene ontology analysis resulted in 37 molecular functions, 79 cellular components, and 129 biological processes were found to be commonly enriched in AD and COVID-19. We identified 26 hub genes which includes AKT1, ALB, BDNF, CD4, CDH1, DLG4, EGF, EGFR, FN1, GAPDH, INS, ITGB1, ACTB, SRC, TP53, CDC42, RUNX2, HSPA8, PSMD2, GFAP, VAMP2, MAPK8, CAV1, GNB1, RBX1, and ITGA2B. Specific miRNA targets associated with Alzheimer's disease and COVID-19 were identified through miRNA target prediction. In addition, we found hub genes-transcription factor and hub genes-drugs interaction. We also performed pathway analysis for the hub genes and found that several cell signaling pathways are enriched, such as PI3K-AKT, Neurotrophin, Rap1, Ras, and JAK-STAT. CONCLUSION: Our results suggest that the identified hub genes could be diagnostic biomarkers and potential therapeutic drug targets for COVID-19 patients with AD comorbidity.