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Matthew P. Frosch
Diagnostic neuropathology of neurodegenerative disease, cerebrovascular disease, brain tumors.
The current major research emphasis in my lab focuses on cerebral amyloid angiopathy (CAA). In this disease, the peptide A-beta deposits in the walls of blood vessels and is associated with risk of hemorrhage (ëlobar hemorrhagesí). 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 through a combination of animal models and investigations of human tissue.
Lab Website: Frosch Lab
Dr. Frosch is the Lawrence J. Henderson Associate Professor of Pathology at Harvard Medical School and the Director of the C.S. Kubik Laboratory for Neuropathology at Massachusetts General Hospital. He is board certified in Anatomic Pathology and Neuropathology, directs the MGH Neuropathology Training Program and is Associate Director of the MGH Pathology Training Program (Research Training). He has been an active diagnostic neuropathologist, handling surgical and autopsy diagnoses for more than 20 years and has served as Core Leader of the Neuropathology Core of the Massachusetts ADRC since 2008. He has served a prior term on the ADC Neuropathology Core Steering Committee; when chair of that committee, he used the annual meeting to explore problematic areas in the then-current diagnostic scheme for assessing AD lesions. This exercise helped lead to the establishment of the working group for the 2012 NIA-Alzheimer Association Criteria. Dr. Frosch was an active participant in the formulation of the new guidelines and a coauthor of the final recommendations.
Dr. Frosch is currently the Vice-President of the American Association of Neuropathologists and has just been elected to another term on the ADC Neuropathology Steering Committee. He serves on the editorial boards of Acta Neuropathologica, Journal of Neuropathology and Experimental Neurology, Neuropathology and Applied Neurobiology (Executive Editor) and is chair of the Scientific Program Committee of the Alzheimer Association International Conference. At Harvard Medical School, Dr. Frosch is Associate Director of the Harvard-MIT Division of Health Sciences and Technology (HST), directs two courses for the HST MD program students (Neuroscience and MatLab for Medicine) and chairs the Admissions Committee. He received both the Donald OíHara Faculty Prize for Excellence in Teaching and the Irving M. London Teaching Award. Dr. Frosch's research program focuses on cerebral amyloid angiopathy and the interface between cerebrovascular disease and neurodegenerative diseases.
Gregory JL, Prada CM, Fine SJ, Garcia-Alloza M, Betensky RA, Arbel-Ornath M, Greeberg SM, Bacskai BJ, Frosch MF. Reducing Available Soluble Beta-Amyloid Prevents Progression of Cerebral Amyloid Angiopathy in Transgenic Mice. J Neuropathol Exp Neurol 2012;71: 1009-1017. [PMCID: 3491571].
Arbel-Ornath M, Hudry E, Eikermann-Haerter K, Hou S, Gregory JL, Zhao L, Betensky RA, Frsoch MP, Greenberg SM, Bacskai BJ. Interstitial Fluid Drainage is Impaired in Ischemic Stroke and Alzheimer's Disease Mouse Models. Acta Neuropathol 2013; 126: 353-364. [PMCID: 3810119].
Serrano-Pozo A, Qian J, Monsell SE, Frosch MP, Betensky RA, Hyman BT. Examination of the Clinicopathologic Continuum of Alzheimer Disease in the Autopsy Cohort of the National Alzheimer Coordinating Center. J Neuropathol Exp Neurol 2013; 72: 1182-1192. [PMCID: 3962953].
Augustinack JC, van der Kouwe AJW, Salat DH, Benner T, Stevens AA, Annese J, Fischl B, Frosch MP, Corkin S. H.M.'s Contributions to Neuroscience: A Review and Autopsy Studies. Hippocampus 2014; 24: 1267-1286. doi: 10.1002/hipo.22354.
Serrano-Pozo A, Qian J, Monsell SE, Blacker D, Gomez-Isla T, Betensky RA, Growdon JH, Johnson K, Forsch MP, Sperling RA, Hyman BT. Mild to Moderate Alzheimer Dementia with Insufficient Neuropathological Changes. Ann Neurol 2014; 75: 597-601. [PMCID: 4016558].
Zhao L, Arbel-Ornath M, Wang X, Betensky RA, Greenberg SM, Frosch MP, Bacskai BJ. Matrix Metalloproteinase 9-Mediated Intracerebral Hemorrhage Induced by Cerebral Amyloid Angiopathy. Neurobiol Aging 2015; 36: 2963-2971.
More publications may be found at www.ncbi.nlm.nih.gov/