Investigation of Inflammatory Responses in the Olfactory System

PROJECT SUMMARY Olfactory loss is a prodromal symptom of neurodegenerative diseases and is also frequently observed in clinical manifestations among COVID-19 patients. Whether the degree of olfactory deficit in COVID-19 is indicative of any long-term neurological diseases has not been carefully evaluated. Recent human studies have identified that SARS-CoV-2 infection is associated with the early onset of Alzheimer's and Parkinson disease. In this study, we created an acute neurodegenerative disease mouse model, which allows us to investigate the impact of neurotoxic aggregates in the olfactory bulb on neuroinflammation and pathology propagation. We hypothesize that viral infection induced inflammation compounds with predisposed neurotoxic aggregates induced inflammation. Specifically, we will characterize inflammatory responses in the olfactory system induced by stereotaxically injected amyloid beta and alpha-synuclein aggregates and further establish SARS-CoV-2 infections paradigms along with the acute neurotoxin model to study molecular and cellular phenotypes between external pathogen exposure and internal protein aggregates induced changes. Through this study, we will gain an understanding of the impact of SARS-CoV-2 infection on neurotoxic aggregate associated neurodegeneration.