Translational CAA Research Lab

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.

Lab Members

Susanne J. van Veluw, PhD (she/her): Principal Investigator, Associate Professor in Neurology (MGH/HMS)
Susanne trained as a neuroscientist in The Netherlands and received her PhD at the University Medical Center Utrecht. She moved to Boston to pursue her post-doctoral training with Drs. Steven Greenberg and Brian Bacskai, after which she joined the department of Neurology as a faculty member. Besides studying the biological mechanisms in CAA disease progression, she has a passion for mentoring trainees and a strong interest in philosophy and ethics.

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, PhD (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.

Thijs W. van Harten, PhD (he/him):  Post-doctoral Research Fellow 
Thijs did his PhD at the department of Radiology of Leiden University Medical Center in the Netherlands on advanced MRI markers of cerebral small vessel disease. His work in our lab will focus on the measurement of the movement of fluids in the brain using MRI and the development of image analysis pipelines.

Alex Andre, PhD (he/him): Program Manager
Alex got his PhD from Arizona State university where he studied the inflammatory role of muscle during repair and how the innate immune system can be modulated to ameliorate dystrophic disease pathology. In our lab he will help manage projects, general lab operations, and clinical research. He also serves as the network administrative officer for the Leducq network on brain clearance in CAA. 

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
Linzsey joined the lab over the summer as a visiting student from Tougaloo College and has continued working with us remotely on projects related to quantifying ischemic tissue injury in CAA.

Lydia K. Mroz (she/her): Undergraduate student
Lydia has joined our lab as a Northeastern Co-op student and is working on optimizing the postprocessing pipelines for ex vivo quantitative susceptibility mapping (QSM) and three-dimensional histology. She is a Northeastern University student pursuing a Bachelor's degree in Behavioral Neuroscience with minors in Computer Science and Math. 

Gabi Poniz: Gabi has recently joined the lab to explore the ethical implications of dementia research, focusing on informed consent, patient disclosure, and the preservation of patient personhood amidst cognitive impairment. She is currently studying Philosophy and Neuroscience at Harvard University.

Affiliated Lab Members

Maria V. Sanchez-Mico, PhD (she/her): Instructor in Neurology
Maria is an Instructor in Dr. Bacskai’s lab. Her research is focused on the role of astroglial dysfunction in Alzheimer’s disease (AD), by monitoring their specific dynamics in vivo over the course of the pathology using two-photon microscopy. In addition, she is also interested in unraveling how specific metabolic pathways are impaired in astrocytes in the living brain of AD and CAA mouse models, specifically during neurovascular coupling. Currently, she is collaborating with us on a project in which we are trying to decipher the mechanism of ARIA (Amyloid Related Imaging Abnormalities), one of the main severe side effects of recently FDA-approved immunotherapies for the treatment of AD.

Francesco Bax, MD: Stroke Research Fellow
Francesco completed his MD at the University of Padova and his Neurology Residency at the Udine University Hospital, Italy. He is currently a Research Fellow in Dr. Steve Greenberg’s lab, where he is focusing his research on serum biomarkers for CAA and Alzheimer’s disease and their correlation with neuroimaging. He is also very interested in exploring CAA related-inflammation (CAA-ri) as a model for amyloid-related imaging abnormalities (ARIA), a side effect of the new anti-amyloid therapies. He is currently collaborating with our lab on this topic, focusing on the neuropathological aspects of CAA-ri.

Alumni

Ashley A. Scherlek, BM
Brittney Moncrieffe, BS
Nazanin Makkinejad, PhD
Emma A. Koemans, MD
Irvin Yi
Jonathan E. Bonilla
Leon P. Munting, PhD
Maarten L. van den Berg, MD
Corinne A. Auger, BM
Whitney M. Freeze, PhD
Lydiane Hirschler, PhD
Lee Maresco, BS
Nicole W. Mumbi 
K. Vi Trinh
Maria Clara Zanon Zotin, MD, PhD

Resources

Cerebral Amyloid Angiopathy Research Program

CAA Forum