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Frosch Lab

My laboratory is interested in the development and characterization of animal models of human neurodegenerative diseases, particularly Cerebral amyloid angiopathy (CAA), Alzheimer and Parkinson diseases.

Matthew P. Frosch, MD, PhD

Associate Pathologist
Director of Neuropathology
Massachusetts General Hospital

Lawrence J. Henderson Associate Professor of Pathology
and Health Sciences and Technology
Harvard Medical School

Research Interests

My laboratory is interested in the development and characterization of animal models of human neurodegenerative diseases, particularly Cerebral amyloid angiopathy (CAA), Alzheimer and Parkinson diseases.

In addition to the activities of my laboratory, I am the faculty coordinator for the tissue-based activities of the Harvard NeuroDiscovery Center (HNDC).  We design the implementation of programs that can support tissue-based research into a wide range of neurodegenerative disorders, as pursued across the Harvard neuroscience community (including basic and clinical investigations). Among the resources we have developed is the Advanced Tissue Resource Center, based in Building 114, which includes a staffed Laser Capture Microdissection facility that is available to users.

I direct the Neuropathology Core of the NIA-supported Massachusetts Alzheimer Disease Research Center (MADRC).  The Core provides diagnostic and research-oriented neuropathology autopsy services in support of the Clinical Core of the MADRC.  It also provides tissue to a wide range of researchers within the institution, across the country and internationally.

 

Title updated 3/4/2013

Laboratory Members

Isabel Costantino, Tech II
Nehal Patel, Tech II

Harvard NeuroDiscovery Center Staff 

Charles Vanderburg, PhD
Ozge Casgal-Getkin, Tech II

The current major research emphasis in my lab focuses on the development of cerebral amyloid angiopathy (CAA) in mouse models. In this disease, the peptide A-beta 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 a recent clinicopathologic study, we have 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. For these reasons, we are interested in learning what the sequence of events is by which the A-beta 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 that have been shown to alter A-beta deposits in the brain.

We are pursuing these studies using multiphoton imaging as applied both ex vivo to fixed brains and in vivo through a glass window placed in the skull. These investigations are to be complemented by a series of immunohistochemical studies and image reconstruction to match the vessel structure and integrity with the 3-dimensional image generated using the multiphoton approach. We also aim to use laser capture microdissection to define alterations in gene expression that occur in smooth muscle cells in the proximity of amyloid deposits of CAA.

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Frosch Laboratory

MassGeneral Institute - Neurodegenerative Disease
Massachusetts General Hospital, B114-2700
114 16th Street
Charlestown, MA 02129

Phone: 617-726-5156
Fax: 617-724-1813


Email: mfrosch@partners.org