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Matthew P. Frosch, MD, PhD
Title: Director, Neuropathology Service, Massachusetts General Hospital & Director, Neuropathology Core, Massachusetts Alzheimer's Disease Research Center & Lawrence J. Henderson Associate Professor of Pathology and Health Sciences and Technology (HST), Harvard Medical School
Telephone: (617) 726-5156
Dr. Frosch received his undergraduate degree in Chemistry (summa cum laude) from Amherst College and his MD and PhD (biophysics) from Harvard University. He was trained in anatomic pathology and neuropathology at the Brigham and Women's Hospital and was a Paul B. Beeson Faculty Scholar in Aging Research from 1999-2002.
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 (‘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 through a combination of animal models and investigations of human tissue.
Freeman SH, Raju S, Hyman BT, Frosch MP, Irizarry MC. Plasma Abeta Levels Do Not Reflect Brain Abeta Levels. J Neuropathol Exp Neurol 2007 ; 66 : 264-271.
Ingelsson M, Ramasamy K, Russ C, Freeman SH, Orne J, Raju S, Matsui T, Growdon JH, Frosch MP, Ghetti B, Brown RH, Irizarry MC, Hyman BT. Increase in the Relative Expression of Tau with Four Microtubule Binding Repeat Regions in Frontotemporal Lobar Degeneration and Progressive supranuclear Palsy Brains. Acta Neuropathol 2007; 114 : 471-479.
Kinnecom C, Lev MH, Wendell L, Smith EE, Rosand J, Frosch MP, Greenberg SM. Course of Cerebral Amyloid Angiopathy-Related Inflammation. Neurology 2007 ; 68: 1411-1416. [PMC Journal - In Process].
Shin HK, Jones PB, Garcia-Alloza M, Borrelli L, Greenberg SM, Bacskai BJ, Frosch MP, Hyman BT, Moskowitz MA, Ayata C. Age-Dependent Cerebrovascular Dysfunction in a Transgenic Mouse Model of Cerebral Amyloid Angiopathy. Brain 2007; 130: 2310-2319. [PMC Journal - In Process].
Freeman SH, Kandel R, Cruz L, Rozkalne A, Newell K, Frosch MP, Hedley-Whyte ET, Locascio JJ, Lipsitz LA, Hyman BT. Preservation of Neuronal Number Despite Age-Related Cortical Brain Atrophy in Elderly Subjects without Alzheimer Disease. J Neuropathol Exp Neurol 2008 ; 67:1205-1212. [PMCID: 2734185].
Freeman SH, Spires-Jones T, Hyman BT, Growdon JH, Frosch MP. TAR-DNA Binding Protein 43 in Pick Disease. J Neuropathol Exp Neurol 2008 ; 67: 62-67.
Greenberg SM, Grabowski T, Gurol ME, Skehan ME, Nandigam RN, Becker JA, Garcia-Alloza M, Prada C, Frosch MP, Rosand J, Viswanathan A, Smith EE, Johnson KA. Detection of Isolated Cerebrovascular Beta-Amyloid with Pittsburgh Compound B. Ann Neurol 2008 ; 64: 587-591. [PMCID: 2605158].
Freeman SH, Hyman BT, Sims KB, Hedley-Whyte ET, Vossough A, Frosch MP, Schmahmann JD. Adult Onset Leukodystrophy with Neuroaxonal Spheroids: Clinical, Neuroimaging and Neuropathologic Observations. Brain Pathol 2009 ;19 : 39-47. [PMCID: 2757058].
Garcia-Alloza M, Prada C, Lattarulo C, Fine S, Borrelli LA, Betensky R, Greenberg SM, Frosch MP, Bacskai BJ. Matrix Metalloproteinase Inhibition Reduces Oxidative Stress Associated with Cerebral Amyloid Angiopathy in vivo in Transgenic Mice. J Neurochem 2009; 109: 1636-1647.
Greenberg SM, Nandigam RN, Delgado P, Betensky RA, Rosand J, Viswanathan A, Frosch MP, Smith EE. Microbleeds Versus Macrobleeds: Evidence for Distinct Entities. Stroke 2009; 40: 2382-2386. [PMCID: 2758289].
Dierksen GA, Skehan ME, Khan MA, Jeng J, Nandigam RN, Becker JA, Kumar A, Neal KL, Betensky RA, Frosch MP, Rosand J, Johnson KA, Viswanathan A, Salat DH, Greenberg SM. Spatial Relation Between Microbleeds and Amyloid Deposits in Amyloid Angiopathy. Ann Neurol 2010: 68: 545-548.
Jun G, Naj AC, Beecham GW et al. Meta-Analysis Confirms CR1, CLU, and PICALM as Alzheimer Disease Risk Loci and Reveals Interactions with APOE Genotypes. Arch Neurol 2010; 67: 1473-1484.
Lu Q, Ding K, Frosch MP, Jones S, Wolfe M, Xia W, Lanford GW. Alzheimer's Disease-Linked Presenilin Mutation (PS1M146L) Induces Filamin Expression and Gamma-Secretase Independent Redistribution. J Alzheimers Dis 2010; 22: 235-245.
Nelson PT, Kukull WA, Frosch MP. Thinking Outside the Box: Alzheimer-Type Neuropathology That Does Not Map Directly Onto Current Consensus Recommendations. J Neuropathol Exp Neurol 2010; 69: 449-454. [PMCID: 2892786].
Serrano-Pozo A, William CM, Ferrer I, Uro-Coste E, Delisle MB, Maurage CA, Hock C, Nitsch RM, Masliah E, Growdon JH, Frosch MP, Hyman BT. Beneficial Effect of Human Anti-Amyloid-Beta Active Immunization on Neurite Morphology and Tau Pathology. Brain 2010; 133: 1312-1327. [PMCID: 2859150].
Arboleda-Velasquez JF, Manent J, Lee JH, Tikka S, Ospina C, Vanderburg CR, Frosch MP, Rodriguez-Falcon M, Villen J, Gygi S, Lopera F, Kalimo H, Moskowitz MA, Ayata C, Louvi A, Artavanis-Tsakonas S. Hypomorphic Notch 3 Alleles Link Notch Signaling to Ischemic Cerebral Small-Vessel Disease. Proc Natl Acad Sci USA 2011; 108: E128-E135. [PMC Journal - In Process].
Chen-Plotkin AS, Martinez-Lage M, Sleiman PM, et al. Genetic and Clinical Features of Progranulin-Associated Frontotemporal Lobar Degeneration. Arch Neurol 2011; 68: 488-497.
Greenberg SM, Frosch MP. Life Imitates Art: Anti-Amyloid Antibodies and Inflammatory Cerebral Amyloid Angiopathy. Neurol 2011; 76: 772-773.
Hoglinger GU, Melhem NM, Dickson DW, et al. Identification of Common Variants Influencing Risk of the Tauopathy Progressive Supranuclear Palsy. Nat Genet 2011; 43: 699-705.
Naj AC, Jun G, Beecham GW, et al. Common Variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with Late-Onset Alzheimer's Disease. Nat Genet 2011; 43: 436-441.
Skoglund L, Matsui T, Freeman SH, Wallin A, Blom ES, Frosch MP, Growdon JH, Hyman BT, Lannfelt L, Ingelsson M, Glaser A. Novel Progranulin Mutation Detected in Two Patients with FTLD. Alzheimer Dis Assoc Disord 2011; 25: 173-178.
More publications may be found at www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed