Brain ACE2 in Alzheimer's disease in relation to COVID-19

Summary/Abstract Currently the world is suffering from the pandemics of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter host cells. Millions of people have been infected with SARS-CoV- 2 and over 1 million people have died of COVID-19 worldwide, causing serious health, economical, and sociological problems. In Ukraine, a low- and middle-income country (LMICs) with a population of 42 million, 400,000 cases have been confirmed with 7,000 deaths. The aging population is highly susceptible to be severely affected by and die of COVID-19. Neurological manifestations have been reported to occur in a large number of COVID-19 patients, suggesting that this disease may also exert the long-term adverse neurological consequences. However, the effects of SARS-CoV-2 on human host cells, particularly those in the brain, have not been defined. Lack of such knowledge interferes with the development of therapeutic strategies to combat COVID-19. The long-term objective of our research is to define the relationships between neurological disorders and COVID-19. We recently found that Alzheimer's disease patients have the upregulated hippocampal ACE2 expression. In this international collaborative exploratory/pilot Fogarty project, we will test the central hypothesis that the oxidative stress in Alzheimer's disease promotes cell signaling and gene expression mechanisms to upregulate ACE2 that in turn increases the infection by SARS-CoV-2 in the brains of these patients. This project will also engage in research capacity building for Ukraine. We plan to accomplish the objective by addressing the following specific aims: (1) Engage in research capacity building for Ukraine, one of low- and middle-income countries; (2) Define the mechanism of ACE2 gene expression in Alzheimer's brain; and (3) Identify the role of brain ACE2 in Alzheimer's disease in relation to COVID-19. This project is innovative because it will address a novel pathology of COVID-19. Results of this project are significant because they are expected to contribute to the development of new therapeutic agents to reduce the mortality and morbidity caused by COVID-19 that occurs largely in the aging population while building the research capacity in Ukraine. .