Susanne Van Veluw, Ph.D.
Neurology, Mass General Research Institute
Assistant Professor of Neurology
Harvard Medical School
Our lab is interested in the crosslinks between cerebral small vessel disease (SVD) and dementia. In our group we use a combination of advanced neuroimaging techniques in human brain tissue and animal models to unravel the histopathological underpinnings of neuroimaging markers of SVD and to get at the pathophysiological mechanisms involved. Our research focuses on cerebral amyloid angiopathy (CAA). Sporadic CAA is one of the two most common forms of SVD affecting the brains of older individuals. CAA is characterized by the accumulation of amyloid β in the walls of leptomeningeal and cortical blood vessels, and frequently co-occurs with parenchymal amyloid β deposits in the brains of patients with Alzheimer’s disease. Patients with severe CAA have increased risk to suffer from symptomatic large intracerebral hemorrhages, which are often fatal. Even in the absence of these catastrophic hemorrhages, the accrual of numerous small silent ischemic and hemorrhagic strokes over time, can lead to cognitive impairment and dementia in affected individuals. Currently there are no effective treatment strategies available to cure or slow down the progression of the disease.
We use a combination of high-resolution ex vivo MRI in human brain tissue and neuropathology to better understand the histopathological nature of SVD lesions in patients with CAA. Using MRI-guided sampling and serial sectioning in areas with microinfarcts and microbleeds, we have been able to identify affected vessels and study the pathological alterations at the single vessel level. Furthermore, we use real-time in vivo two-photon microscopy in mouse models of CAA to study early functional alterations of CAA-affected vessels. This powerful experimental approach allows us to track individual vessels over time and gives us the opportunity to identify targets for early intervention strategies. Moreover, with this translational approach we can test clinical observations directly in the lab and vice versa.
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