The focus of our research is to elucidate common mechanisms of vascular dysfunction and cognitive decline in neurodegenerative disease. The vascular network and brain blood flow are crucial to supply the brain with oxygen and nutrient to exert proper function.
Although it has been known for many years that vascular dysregulation and cerebral blood flow (CBF) reductions are involved in neurodegeneration and stroke, the underlying mechanisms leading to CBF reductions are only beginning to be understood.
What cells of the neurovascular unit mediating the signaling leading to CBF reductions and vascular inflammation?
what are the common/shared mechanisms driving CBF reduction in neurodegenerative disease?
What are functional connections between the incidence of stroke/microhemorrhages, and Alzheimer’s disease?
What is the role of the immune system in CBF reduction?
Although all neurological disorders have distinct pathological aspects (e.g., amyloid plaques in Alzheimer’s disease, AD), recent evidence suggests that all neurodegenerative disorders such as AD, Parkinson’s disease, and other forms of dementia may share a common pathology: vascular dysfunction. Dysfunctional microcirculation may be a critical contributing factor of these neurodegenerative disorders due to 1) a loss or alteration of vascular cells such as endothelial cells, leukocytes, and pericytes, 2) molecular changes within the vascular cells of the neurovascular unit, and/or 3) inherited genes that may predispose individuals to cerebral vascular abnormalities. Classically, research focused on the neuronal aspect of those diseases, sometimes to the exclusion of another hypothesis. It is well known that the circulatory system is crucial for neuronal health and vice versa. However, this view does not consider that the essential cells of the neurovascular unit and the circulatory system are also involved during pathogenesis and may even be crucial for the initiation and progression of neurodegenerative disease and ischemic lesions caused by a stroke, a known risk factor for neurodegenerative disease.
To achieve these goals, we will utilize novel second-generation models of neurodegenerative disease combined with high spatial and high temporal in vivo multiphoton imaging, behavioral experiments, and post mortem analyses.