Dr. Zlokovic studies the role of brain microcirculation, particularly the blood-brain barrier (BBB) in health and disease in the adult brain and during brain aging. He made major contributions to our understanding of the role of BBB in the pathogenesis and treatment of Alzheimer’s disease (AD) and stroke.

Using animal models and studying human brain, his laboratory has shown that dysfunction in the BBB and brain microcirculation can accumulate before neuronal loss, and is an early biomarker of human cognitive dysfunction.

His group showed that disrupted cross-talk between BBB-associated pericytes and brain capillary endothelial cells, and astrocytes and pericytes, within the neurovascular unit leads to neuronal dysfunction in both synapses and neurons, and that targeting the BBB cellular and molecular pathways can slow down, arrest and of prevent development of a neurodegenerative process.

He has identified genes and receptors at the BBB that regulate brain levels of Alzheimer’s amyloid-beta toxin, which accumulates with aging and dementia.

More recently, his team has developed new imaging techniques for studying BBB function in animal models and the living human brain. These findings contributed to development of Phase 2/3 clinical trials for AD patients.

He co-discovered with J.H. Griffin vasculoprotective, neuroprotective, and anti-inflammatory activities of activated protein C (APC) in the CNS, including the receptor requirements and downstream signaling pathways.