Kavli Affiliate: Robert Edwards
| Authors: Susana Furman, Latifa Zayou, Kate I Inman Tsourmas, Dominic Ibarra Javonillo, Gema M Olivarria, Yuting Cheng, Collin Pachow, Kellie Fernandez, Lucas Le, Robert Andrew Edwards, Dequina Nicholas, Gabriela Pacheco Sanchez, Ralph S. Baric, Kim N Green and Thomas E. Lane
| Summary:
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia. It is characterized by cognitive decline and accumulation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Accumulating evidence indicates that viral infection may worsen and/or increase development of established AD pathology. The COVID-19 pandemic has brought attention to the link between SARS-CoV-2 infection and neurologic conditions that vary in severity and duration, as well as the worsening of clinical symptoms in elderly people with dementia. To better understand potential mechanisms by which SARS-CoV-2 infection impacts AD neuropathology, aged 5xFAD and wildtype (WT) mice were intranasally infected with mouse-adapted SARS-CoV-2 (MA10). Intranasal infection of aged-matched (10-14 month) 5xFAD or wild type (WT) C57BL/6 mice with MA10 resulted in viral infection of the lungs that correlated with acute viral pneumonia characterized by lymphocyte inflammation and antiviral immune responses. Viral RNA was not detected within the central nervous system (CNS) of either WT or 5xFAD mice at days 7 or 21 post-infection (p.i.), nor were there signs of overt glial activation or neuroinflammation. There were no differences in either Aβ plaque volume or number within the brains of MA10-infected 5xFAD mice compared to uninfected 5xFAD mice. However, bulk RNA sequencing and spatial transcriptomics revealed evidence of altered expression of genes associated with neuronal and glial dysfunction, as well as reduced expression of genes encoding adhesion molecules in vascular endothelial cells. Collectively, these findings demonstrate that MA10 infection did not affect Aβ plaque size or numbers in 5xFAD mice, yet in both WT and 5xFAD mice, there were numerous down-stream effects on gene expression associated with resident CNS cell function.