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

Area of Science:

• Neuroscience
• Genomics
• Infectious Diseases

Background:

• Cognitive decline is a frequent outcome of COVID-19.
• Emerging evidence suggests a connection between COVID-19 and Alzheimer's disease (AD).
• The precise molecular mechanisms linking COVID-19 to AD remain largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying the association between COVID-19 and AD.
• To identify potential genetic targets for pharmaceutical interventions against COVID-19-related neurological conditions.

Main Methods:

• Transcriptome datasets from 638 brain samples were analyzed.
• Robust Rank Aggregation, functional enrichment, and network analyses were employed.
• Commonly altered genes, miRNAs, and transcription factors in AD and COVID-19 brains were identified.

Main Results:

• Commonly altered pathways in both AD and COVID-19 brains include downregulated cyclic adenosine monophosphate (cAMP) signaling and taurine metabolism.
• Neuroinflammatory pathways were found to be upregulated in both conditions.
• Gene-miRNA and gene-transcription factor networks revealed potential regulatory mechanisms.

Conclusions:

• Shared pathway alterations, including reduced cAMP signaling and increased neuroinflammation, may increase COVID-19 patients' susceptibility to cognitive decline and AD.
• Identified genetic targets offer potential for pharmaceutical strategies to mitigate neurological risks associated with COVID-19 and AD.