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 , and . 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.