AUTHOR=Fu Yifan , Guo Zhirong , Wang Yulin , Zhang Haonan , Zhang Feifan , Xu Zihao , Shen Xin , Roppongi Reiko T. , Mo Shaocong , Gu Wenchao , Nakajima Takahito , Tsushima Yoshito TITLE=Single-nucleus RNA sequencing reveals the shared mechanisms inducing cognitive impairment between COVID-19 and Alzheimer’s disease JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.967356 DOI=10.3389/fimmu.2022.967356 ISSN=1664-3224 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.