Unraveling the connection between Alzheimer's Disease and COVID-19

Common Molecular Signatures Between Coronavirus Infection and Alzheimer’s Disease Reveal Targets for Drug Development

Background: Cognitive decline is a common consequence of COVID-19, and studies suggest a link between COVID-19 and Alzheimer’s disease (AD). However, the molecular mechanisms underlying this association remain unclear. Objective: To understand the potential molecular mechanisms underlying the association between COVID-19 and AD development, and identify the potential genetic targets for pharmaceutical approaches to reduce the risk or delay the development of COVID-19-related neurological pathologies. Methods: We analyzed transcriptome datasets of 638 brain samples using a novel Robust Rank Aggregation method, followed by functional enrichment, protein-protein, hub genes, gene-miRNA, and gene-transcription factor (TF) interaction analyses to identify molecular markers altered in AD and COVID-19 infected brains. Results: Our analyses of frontal cortex from COVID-19 and AD patients identified commonly altered genes, miRNAs and TFs. Functional enrichment and hub gene analysis of these molecular changes revealed commonly altered pathways, including downregulation of the cyclic adenosine monophosphate (cAMP) signaling and taurine and hypotaurine metabolism, alongside upregulation of neuroinflammatory pathways. Furthermore, gene-miRNA and gene-TF network analyses provided potential up- and downstream regulators of identified pathways. Conclusion: We found that downregulation of cAMP signaling pathway, taurine metabolisms, and upregulation of neuroinflammatory related pathways are commonly altered in AD and COVID-19 pathogenesis, and may make COVID-19 patients more susceptible to cognitive decline and AD. We also identified genetic targets, regulating these pathways that can be targeted pharmaceutically to reduce the risk or delay the development of COVID-19-related neurological pathologies and AD.