Neuronal activity modulation and age-related neurodegeneration - Abstract 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.