Single-nucleus RNA sequencing reveals the shared mechanisms inducing cognitive impairment between COVID-19 and Alzheimer's disease

Front Immunol. 2022 Sep 23:13:967356. doi: 10.3389/fimmu.2022.967356. eCollection 2022.

Abstract

Alzheimer's disease (AD)-like cognitive impairment, a kind of Neuro-COVID syndrome, is a reported complication of SARS-CoV-2 infection. However, the specific mechanisms remain largely unknown. Here, we integrated single-nucleus RNA-sequencing data to explore the potential shared genes and pathways that may lead to cognitive dysfunction in AD and COVID-19. We also constructed ingenuity AD-high-risk scores based on AD-high-risk genes from transcriptomic, proteomic, and Genome-Wide Association Studies (GWAS) data to identify disease-associated cell subtypes and potential targets in COVID-19 patients. We demonstrated that the primary disturbed cell populations were astrocytes and neurons between the above two dis-eases that exhibit cognitive impairment. We identified significant relationships between COVID-19 and AD involving synaptic dysfunction, neuronal damage, and neuroinflammation. Our findings may provide new insight for future studies to identify novel targets for preventive and therapeutic interventions in COVID-19 patients.

Keywords: AD-high-risk scores; Alzheimer’s disease; SARS-CoV-2; cognitive impairment; neuroinflammation; single-nucleus RNA sequencing.

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • COVID-19* / complications
  • COVID-19* / genetics
  • Cognitive Dysfunction* / genetics
  • Genome-Wide Association Study
  • Humans
  • Proteomics
  • RNA
  • SARS-CoV-2
  • Sequence Analysis, RNA

Substances

  • RNA