Frontiers in Immunology (Sep 2022)

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

  • Yifan Fu,
  • Yifan Fu,
  • Zhirong Guo,
  • Yulin Wang,
  • Haonan Zhang,
  • Feifan Zhang,
  • Zihao Xu,
  • Xin Shen,
  • Reiko T. Roppongi,
  • Shaocong Mo,
  • Wenchao Gu,
  • Wenchao Gu,
  • Takahito Nakajima,
  • Yoshito Tsushima

DOI
https://doi.org/10.3389/fimmu.2022.967356
Journal volume & issue
Vol. 13

Abstract

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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.

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