Matthew Frosch, MD, PhD
Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School
Dr. Frosch serves as Co-Lead for the ACTC Neuropathology Unit. He is the Lawrence J. Henderson Associate Professor of Pathology and Health Sciences & Technology at Harvard Medical School, and Director of the C.S. Kubik Laboratory for Neuropathology at Massachusetts General Hospital, for the MassGeneral Institute for Neurodegenerative Diseases (MIND) Dr. Frosch’s lab aims to understand cerebral amyloid angiopathy (CAA), using mouse models and human tissue. In this disease, the peptide Ab deposits in the walls of blood vessels and is associated with risk of hemorrhage (“lobar hemorrhages”). This peptide is the same material that forms the plaques of Alzheimer disease, and nearly all patients with Alzheimer disease have pathologic evidence of CAA as well. CAA also occurs in the absence of histologic evidence of Alzheimer disease, and can present with hemorrhages or with cognitive changes. In clinicopathologic studies, his lab has found that this latter presentation is associated with the presence of an inflammatory response, often containing giant cells. This subset of patients can have dramatic recoveries of cognitive function after immunosuppressive therapy. Dr. Frosch and his team are interested in the sequence of events by which Ab is deposited in blood vessels, what factors determine the distribution of involvement, what the consequences are for the cells of the vessel and how this material can respond to therapeutic interventions focused on Ab currently in clinical trials. For in vivo studies, Frosch’s team uses serial multiphoton imaging with specific probes for these various processes and link the spatial and temporal distribution of the pathologic changes with the development of CAA. They complement these studies with work on human autopsy tissue, collected through the Massachusetts Alzheimer Disease Research Center Neuropathology Core. Those samples are examined through combinations of high field ex vivo MRI, optical clearing and volumetric imaging. They are particularly interested in the changes which result in bleeding in the setting of CAA (hemorrhagic strokes) as well as microinfarcts which can markedly impair cognition. Dr. Frosch also works with a range of collaborators to understand the relationship between neuropathologic findings in the setting of disease — including Alzheimer disease, Parkinson disease, Amyotrophic Lateral Sclerosis and others — and other biochemical or functional markers of disease. These studies include advancing imaging methods (DTI, OCT and others) as well as various genetic studies (deep sequencing as well as GWAS), cell biology and structural biology.