Innate Immune Responses to SARS-CoV-2 in AD mouse models

University Of California At Davis, Davis CA

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Abstract

RESEARCH SUMMARY Sudden-onset of olfactory loss has been recognized as a common COVID-19 symptom during the early phase of the pandemic. Whether the degree of olfactory deficit in COVID-19 is indicative of any long-term neurological diseases has not been carefully evaluated. Olfactory dysfunction is well recognized as an early symptom of dementia, particularly in Alzheimer’s and Parkinson’s diseases. Recent human study identified that SARS-CoV-2 infection is associated with early onset of Alzheimer’s disease. Using mouse models, we observed expanded inflammatory responses in the olfactory epithelium upon sparse SARS-CoV-2 infection. Widespread olfactory receptor downregulation has been reported under viral infection suggesting that there might be a distributed viral impact from localized viral infection in the olfactory epithelium. We hypothesize that widespread the inflammatory response in the olfactory epithelium, triggered by SARS-CoV-2, enhances the impact of familial Alzheimer’s disease mutations resulting accelerated disease progression. In this study, we will characterize inflammatory responses to SARS-CoV-2 in the olfactory epithelium and the olfactory bulb in Alzheimer’s disease mouse models; and we will further determine SARS-CoV-2 infection induced olfactory functional deficits in AD mouse models. Through this study, we will gain understanding of genetic background dependent molecular and histological changes upon SARS-CoV-2 infection. This pilot study will also establish premise for using olfactory pathway as an entry point to investigate the molecular mechanisms involved in Alzheimer’s disease pathogenesis.