New research from the University of Rochester Medical Center (URMC) aims to uncover how HIV contributes to brain health issues, even in patients effectively treated with antiretroviral therapy. Scientists are focusing on a protein called Delta-like 4 (Dll4) and its role in damaging the brain’s microscopic blood vessels, potentially leading to strokes, memory problems, and cognitive decline.
The study, supported by the National Institute of Neurological Disorders and Stroke, is led by neurologist Dr. Giovanni Schifitto and cardiovascular biologist Dr. Jinjiang Pang. Their work builds on previous findings linking chronic inflammation in people with HIV to cerebrovascular disease and disruptions in brain structure and function.
Dr. Schifitto and his team, including researchers Nasir Uddin, PhD, Mia Weber, PhD, and Xing Qiu, PhD, recently published a paper in Scientific Reports. They demonstrated that advanced MRI techniques, particularly tensor-valued imaging, can detect subtle brain microstructural changes associated with HIV. The imaging technique proved highly effective in identifying damage linked to cognitive impairment, positioning it as a promising biomarker for HIV-associated neurocognitive disorders.
The new research will expand on these findings by examining how Dll4, a protein usually expressed in blood vessel endothelial cells, contributes to brain damage. While Dll4 is typically associated with maintaining vascular health, immune cells called monocytes can also release it. In people with HIV, persistent inflammation keeps Dll4 levels elevated, even with antiretroviral treatment.
Dr. Pang’s earlier studies in animal models revealed that Dll4 can alter blood vessel integrity, potentially harming the brain’s vascular network. The current research will use advanced imaging techniques to study brain microcirculation and investigate how monocyte-derived Dll4 interacts with blood vessels in the brain.
The team will also conduct in vitro studies using blood cells from individuals with and without HIV to better understand the molecular mechanisms controlling Dll4 expression and its effect on brain health.
Researchers hope their findings will pave the way for new treatments to prevent or manage cerebrovascular diseases in people living with HIV. With aging being a factor in monocyte activation, the study’s insights may also apply to brain health challenges associated with aging populations.
Additional contributors to the study include Hongmei Yang, PhD, in Biostatistics and Computational Biology, and Shumin Wang, PhD, from Dr. Pang’s lab.
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