Translational CAA Research Lab
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About Our Research
Our lab is interested in the crosslinks between cerebral small vessel disease (SVD) and dementia. 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.
Our lab uses translational imaging approaches, ranging from ex vivo MRI-guided histopathology in human brain tissue to in vivo two-photon microscopy in mice to better understand the pathophysiology of sporadic and hereditary CAA. In particular, we are interested in unraveling the mechanisms of hemorrhage formation in CAA and studying the driving force of perivascular amyloid β clearance, with the goal to find novel targets for therapeutic intervention aimed at preventing hemorrhagic stroke and cognitive impairment in patients with SVD.
Our lab welcomes people from various backgrounds (including professional backgrounds, race, ethnicity, religion, gender identity or expression), as we believe that cultivating an inclusive work environment, where everyone can thrive, is essential to perform rigorous and groundbreaking science.
Susanne J. van Veluw, PhD (she/her): Principal Investigator, Associate Professor in Neurology (MGH/HMS)
Mariel G. Kozberg, MD, PhD (she/her): Instructor in Neurology, Vascular Neurology Attending
Mariel is a vascular neurologist at Mass General Brigham, where she completed her neurology residency and vascular neurology fellowship. She completed her MD and PhD degrees at Columbia University. Mariel’s current research focuses on vascular pathophysiology in cerebral amyloid angiopathy (CAA). She examines the neurovascular unit in mouse models of CAA through longitudinal 2-photon microscopy and widefield optical imaging. Mariel is also interested in the relationship between brain inflammation and hemorrhage in CAA, which she studies in both human tissue and mouse models.
Orla Bonnar, PhD (she/her): 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 continued to study the effects of ApoE on the vasculature, with particular focus on brain clearance and in the context of CAA. In tandem, she uses 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.
Valentina Perosa, MD (she/her): Instructor in Neurology
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 trained 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.
Hilde van den Brink, PhD (she/her): Post-doctoral Research Fellow
Hilde has a background in neuropsychology and neuroscience and recently obtained her PhD at the University Medical Center Utrecht, the Netherlands. In her PhD she used advanced 7Tesla MRI to study small vessel function in patients with cerebral small vessel disease to better understand the mechanisms that drive the brain tissue damage seen in these patients. In our lab, Hilde continues to unravel underlying disease mechanisms, both with in vivo as well as ex vivo MRI and histology.
S. Eugene Kim, BS (she/her): Research Technician I
Eugene's work focuses on assisting the investigation of mechanisms of hemorrhage in mouse models using two-photon microscopy, wide field microscopy, and immunohistochemistry. She graduated from UConn with a bachelor's degree in biological sciences, where she studied genetic mutations in potassium channels implicated in developmental encephalopathy.
Kali vom Eigen, BA (they/she): Research Technician I
Kali assists with neuroimaging techniques in the human brain, including immunohistochemistry, MRI scanning, and image analysis using deep learning software. They hold a bachelor’s degree in biology from Vassar College and hope to pursue a master’s degree in the near future.
L. Linzsey Lyle (she/her): Undergraduate Student
Affiliated Lab Members
Whitney M. Freeze, PhD (she/her): 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.
Maria Clara Zanon Zotin, MD (she/her): Post-doctoral Research Fellow (University of São Paulo, Brazil)
Clara is a neuroradiologist and post-doctoral researcher at the University of São Paulo working on conventional and diffusion-based neuroimaging markers in cerebral amyloid angiopathy. Clara is particularly interested in how diagnostic MRI features of CAA perform in different clinical contexts.
Lydiane Hirschler, PhD (she/her): Post-doctoral Research Fellow (Leiden University Medical Center, the Netherlands)
Lydiane is a post-doctoral researcher at the Leiden University Medical Center in the Netherlands. She focuses on understanding how cerebrospinal fluid (CSF) circulates in human perivascular spaces. To this end, she mainly develops new MRI techniques to measure CSF motion in the human brain.
Ashley A. Scherlek, BM
Brittney Moncrieffe, BS
Nazanin Makkinejad, PhD
Emma A. Koemans, MD
Jonathan E. Bonilla
Leon P. Munting, PhD
Maarten L. van den Berg, MD
Corinne A. Auger, BM
Lee Maresco, BS
Nicole W. Mumbi
K. Vi Trinh
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.