of proposed studies under the Administrative Supplement in response to NOT- AG-20-022 Age is a significant risk factor in the recent SARS-CoV-2 pandemic and this risk might be more profound in middle-aged people with age-related cognitive decline, neurodegeneration and Alzheimer?s disease. While working directly with the SARS-CoV-2 virus is valuable, it requires working in an ABSL-3 level facility and substantially restricts potential behavioral and cognitive studies, brain imaging experiments, and postmortem studies with non-perfused tissues. SARS- CoV-2 recombinant virus-like particles (VLPs) offer an attractive way to study the pathogenesis of SARS-CoV-2 in animals, without the involvement of replicating viruses. In this study, we expose wild-type and human tau mice to SARS-CoV-2 VLPs to study the effects on cognitive performance, brain activity, markers of inflammation, and the effect of sex on the expected degeneration. This study will provide the first data on potential central nervous system complications of Alzheimer?s disease patients, as well as an age-matched population, which are exposed to SARS-CoV-2 VLPs, and will provide an experimental platform to test potential treatments.
Age is a significant risk factor in the recent SARS-CoV-2 pandemic and this risk might be more profound in middle-aged people with age-related cognitive decline, neurodegeneration, and Alzheimer?s disease. While working directly with the SARS-CoV-2 virus is valuable, it requires working in an ABSL-3 level facility and substantially restricts potential behavioral and cognitive studies, brain imaging experiments, and postmortem studies with non-perfused tissues. SARS- CoV recombinant virus-like particles (VLPs) offer an attractive way to study the pathogenesis of SARS-CoV-2 in animals, without the involvement of replicating viruses in an ABSL-1 level facility. In this study, we will expose middle-aged htau and wild-type mice to SARS CoV-2 VLPs and will study if they affect their cognitive performance and neuronal activity.
