Sabharwal to explore mechanisms of cardiovascular and cognitive comorbidities with aging

Rasna Sabharwal, PhD, assistant professor in Cardiovascular Medicine, has received a new two-year $250,000, R21 grant from the National Institute of Health (NIH) for her project “RAS-Driven Central Inflammation and Cognitive Decline with Aging.” This Exploratory/Developmental Research Grant will support Sabharwal’s research to study age-associated mechanisms that contribute to autonomic dysfunction and cognitive decline in apolipoprotein E4 (ApoE4). 

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. “ApoE4 is a well-recognized genetic risk factor in the development of late-onset AD; yet we do not fully understand how it contributes to dementia,” Sabharwal said. The human APOE gene has 3 common variants – ApoE2, ApoE3, and ApoE4. “We are working with human ApoE-knockin mice, and have found that female ApoE4 mice develop reductions in spatial learning and memory, hypertension, and increases in sympathetic tone at older ages,” Sabharwal said. “This robust finding led to our search for the mechanisms involved. 

Sabharwal says that her team has been in collaboration with Keith Michael Sullivan, MD, at Duke University. “We have generated novel transgenic mouse strains to define central signaling pathways involved in the cardiovascular-autonomic and cognitive changes occurring with age.” Through this research, Sabharwal says the team will be able to understand molecular and physiological basis of age-associated pathologies in AD and related dementias.

This is Sabharwal’s second active NIH grant. In early 2020, she received a four-year $2.1M R01 grant from the National Heart, Lung, and Blood Institute to study underlying mechanisms and neural circuitry of stress-induced sudden cardiac death in dilated cardiomyopathy.

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