SARS-CoV-2 Infection, Neuroimmune Response and Risk of Alzheimer’s Disease
Abstract:
While the most severe phase of the Covid-19 pandemic caused by SARS-CoV-2 has subsided, the dreadful post-acute sequelae of Covid-19 (PASC), aka long-Covid, has emerged, even in people who had mild disease. Approximately 10% Covid-19 survivors suffer from persistent neurological impairment with unclear mechanisms. Notably, long-Covid is more prevalent in women although men account for a higher proportion of severe acute SARS-CoV- 2 infections. Further, people carrying the APOE4 gene, the greatest genetic risk factor for late-onset Alzheimer’s disease (AD), exhibit higher severity and mortality post infection than APOE3 carriers. AD patients are prone to Covid-19 and experience worse outcomes than non-AD individuals. Using genetically modified/humanized mouse models, we found that age, sex and APOE genotype modify both peripheral and central immune responses to and recovery from SARS-CoV-2 infection. Despite no detectable virus in the brain, mild SARS-CoV-2 infection accelerates cognitive impairment in AD mice with long-lasting consequences on multiple molecular pathways, including metabolic and mitochondrial pathways as well as immune functions. Our findings suggest that SARS-CoV-2 interacts with risk factors of AD, precipitating the development of neuro-PASC and vice versa.

Bio:
Ling Li, PhD is a Professor in the Department of Experimental and Clinical Pharmacology and the VFW Endowed Chair in Pharmacotherapy for the Elderly in the College of Pharmacy at the University of Minnesota (UMN), with joint faculty appointments in the Neuroscience and Molecular Pharmacology and Therapeutics graduate programs in the Medical School of UMN. The research in Dr. Li’s laboratory centers on the connections between Alzheimer’s disease (AD) and vascular disorders, particularly on the roles of cholesterol/lipoprotein-related pathways in the pathogenesis of AD and their therapeutic implications. Ongoing research projects include the impact of SARS-CoV-2 infection and its interaction with APOE on cognitive function and neuropathology in aging and AD, interplay of mitochondrial lipidomic dynamics and APOE4 in pathogenic brain aging and AD, modulation of systemic and neuroinflammation against the development of AD, and the role of microglial TREM2 in cerebral amyloid angiopathy (CAA) and related pathologies. Dr. Li’s research has been supported by the National Institutes of Health and private foundations. As an educator, Dr. Li is also actively involved in directing/teaching courses in graduate and professional programs as well as mentoring graduate students, professional PharmD/MD students, postdoctoral fellows, and visiting scientists.
Date: 14 January 2025, 13:00
Venue: This event is hybrid
Speaker: Ling Li (University of Minnesota)
Organising department: Nuffield Department of Women's and Reproductive Health
Organiser: Michael Suttie (NDWRH, University of Oxford)
Organiser contact email address: seminars@wrh.ox.ac.uk
Booking required?: Recommended
Booking email: seminars@wrh.ox.ac.uk
Audience: Members of the University only
Editor: Isobel Way