Single-nucleus RNA sequencing reveals the shared mechanisms inducing cognitive impairment between COVID-19 and Alzheimer’s disease
Yifan Fu, Zhirong Guo, Yulin Wang, Haonan Zhang, Feifan Zhang, Zihao Xu, Xin Shen, Reiko T. Roppongi, Shaocong Mo, Wenchao Gu, Takahito Nakajima, Yoshito Tsushima
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.