2023 Alzheimer’s Association Leveraging Model & Data Resources to Advance Alzheimer’s and Dementia Discovery Program (ALZDISCOVERY)
Use of MODEL-AD Mice to Assess Effect of Coronavirus Infection on Pathology
How may contracting COVID-19 promote one’s risk for Alzheimer’s?
Thomas Lane, Ph.D.
University of California, Irvine
Irvine, CA - United States
Background
SARS-CoV-2, the coronavirus responsible for COVID-19, is known to promote lung damage in certain individuals. Research also indicates that the disease may increase one’s risk for developing Alzheimer’s and other dementias. In initial studies with mice engineered to develop Alzheimer’s-like brain changes, Dr. Thomas E. Lane and colleagues found that SARS-CoV-2 infection could increase levels of disease-related tau and beta-amyloid in the animals’ brains. These protein molecules can accumulate into tau tangles and beta-amyloid plaques, two hallmarks of Alzheimer’s. The researchers also found that the mice experienced damage to synapses (the specialized structures that nerve cells use to send signals to one another), loss of nerve cell communication and an increase in anxiety and other behavioral problems. Such findings suggest that coronavirus infection can promote dementia risk in multiple ways.
Research Plan
Dr. Lane and team will work to confirm and expand on their earlier results utilizing a new mouse model that can develop both disease-related tau and beta-amyloid in its brain. First, the investigators will infect the animals with a mouse-adapted version of SARS-CoV-2 and assess how that infection affects tau and beta-amyloid levels, as well as brain cell damage and behavioral and cognitive (brain function) decline. They will also examine whether SARS-CoV-2 infection may alter the activity of microglia (the immune cells of the brain) and promote dementia-related brain inflammation. Next, Dr. Lane and colleagues will look for molecular mechanisms that may underlie the links between SARS-CoV-2 and Alzheimer’s risk. This work will involve identifying dementia-related genes in the brain cells of mice exposed to SARS-CoV-2.
Impact
Dr. Lane’s study could shed new light on the role of COVID-19 in brain health. It could also lead to novel therapies – including genetic therapies – that may reduce the risk COVID-related brain disease.