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About Our Research
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.
Susanne J. van Veluw, PhD: Principal Investigator, Assistant Professor in Neurology (MGH/HMS)
Orla Bonnar, PhD: Post-doctoral research fellow
Orla joined the lab after completing her PhD at the University of Sussex where she investigated the effect of ApoE4 on neurovascular coupling using two-photon microscopy. In our lab she will continue to study the effects of ApoE on the vasculature, with particular focus on brain clearance and in the context of CAA. In tandem, she will use in vivo imaging to better understand some of the mechanisms that underlie brain clearance and how they may be targeted in models of CAA and Alzheimer’s disease.
Mariel G. Kozberg, MD, PhD: Post-doctoral research fellow, vascular neurology fellow
Mariel is a vascular neurology fellow at Mass General Brigham, where she recently completed her neurology residency training. Mariel’s research focuses on the relationship between amyloid β deposition in cerebral amyloid angiopathy (CAA) and underlying vascular physiology. She examines the neurovascular unit in mouse models of CAA through longitudinal, awake 2-photon microscopy. Mariel is also interested in the relationship between brain inflammation and hemorrhage in CAA, which she studies in both human tissue and mouse models.
Leon P. Munting, PhD: Post-doctoral research fellow
Leon is a postdoc from Leiden University who is interested in the two-way relationship between vascular health and amyloid β accumulation in the brain. To that end, his current studies involve the manipulation of vascular physiology in mouse models of amyloidosis using novel techniques such as calcium imaging and optogenetics.
Valentina Perosa, MD: Post-doctoral research fellow
Valentina’s main interest is to explore how cerebral small vessel disease contributes to cognitive impairment. After completing medical school at the University of Magdeburg, she began training as a neurologist and focused her research on ageing and neurodegenerative disease. As a postdoc, Valentina currently investigates enlarged perivascular spaces in patients with CAA, combining post-mortem MRI and histopathology. With this work, we aim to gain more insight in the clearance mechanisms of amyloid β in CAA, which could have repercussions in better understanding the interactions between vascular and Alzheimer’s pathology.
Corinne A. Auger, BM: Research Technician I
Corinne performs histopathology and maintains the mouse colony as the research technician for the van Veluw lab. She holds a degree in violin performance from the Cleveland Institute of Music with minors in music history and chemistry from Case Western Reserve University.
Affiliated Lab Members
Whitney M. Freeze, PhD: Post-doctoral research fellow (Leiden University Medical Center, the Netherlands)
Whitney is our external postdoc and collaborator from the Netherlands working at the Leiden University Medical Center. She focuses on a hereditary variant of CAA called ‘Dutch-type CAA’. She examines CAA-related vascular abnormalities with high-resolution ex vivo MRI and histology to unravel potential pathways that lead to (micro-)vascular lesion formation in both the Dutch-type and sporadic variant of CAA. In addition, she is very interested in the role of blood-brain barrier leakage in CAA.
Lydiane Hirschler, PhD: Visiting post-doctoral research fellow (Leiden University Medical Center, the Netherlands)
Irvin Yi: Undergraduate Research Assistant (Harvard University Class of 2023)
Ashley A. Scherlek, BM
A cortical hemorrhage in a CAA case
Depicted are Iron-positive deposits on a Perls’ Prussian blue stain in the cortex of a CAA case, indicative of an old small hemorrhage.
Intravascular bolus injection of a fluorescent dye
This movie shows the arrival of a fluorescent tracer in the cerebrovasculature of a mouse through a chronic cranial window.
Two-photon microscopy of advanced CAA in a mouse
A maximum intensity projection of CAA-affected blood vessels in a 20-month old APP23 mouse through a chronic cranial window.
Ex vivo MRI scan of human brain tissue
This is a high resolution ex vivo MRI scan (75um resolution) of a piece of brain tissue from a CAA case with numerous microhemorrhages.