511 Whitehead Bldg., 615 Michael St.
Atlanta, GA 30322
404 712-8352 Phone
Co-Leader, Neuropathology Core, Emory ADRC
B.S. Biology, Cornell University, 1977 - 1981
M.S. Biology, Emory University, 1982 - 1984
Ph.D. Neuroscience, Univ. Wisconsin-Madison, 1984 - 1989
- The overlap among neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease
There is considerable clinical and neuropathologic overlap among neurodegenerative diseases. Lewy bodies are frequently found in the brains of patients with Alzheimer's disease, and Parkinson's disease patients frequently show Alzheimer's disease at autopsy in addition to their Parkinson's disease. In addition, there in considerable clinical and neuropathologic heterogeneity and overlap in the family of diseases known as "tauopathies". We are interested in the pathogenetic mechanisms underlying these diseases and in how these mechanisms interact with one another.
- Regional differences in amyloid deposition, processing and association with apolipoprotein E
While the neocortex displays both neuritic and diffuse plaques in Alzheimer's disease, plaques in the the striatum and cerebellum are predominantly, if not exclusively diffuse, regardless of disease duration. Furthermore, ApoE colocalizes with a subset of plaques in the neocortex and cerebellum, but not in the striatum. Neurofibrillary pathology in the neocortex is typically abundant in throughout much of the neocortex, but the occipital cortex is often relatively, if not entirely, spared. Such regional differences are not only intriguing, but an understanding of the factors underlying these differences could shed light on the pathogenesis of Alzheimer's disease.
Honorable Mention, Moore Aware for best paper on clinicopathologic correlation at the annual meeting of the American Association of Neuropathologists, 2004
Moore Award for the best paper on clinicopathologic correlation at the annual meeting of the American Association of Neuropathologists, 1998
National Science Foundation Graduate Fellowship, 1983-1986
Choi J, Sullards MC, Olzmann JA, Rees HD, Weintraub ST, Bostwick DE, Gearing M, Levey AI, Chin L-S, Li L. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J Biol Chem 2006;281:10816-10824.
Momeni P, Cairns NJ, Perry RH, Bigio EH, Gearing M, Singleton AB, Hardy J. Mutation analysis of patients with neuronal intermediate filament inclusion disease (NIFID). Neurobiol Aging 2006;27:778.e1-778.e6.
Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst C-A, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH. A mutation of b-actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am J Hum Genet 2006;78:947-960.
Dodson SE, Gearing M, Lippa CF, Montine TJ, Levey AI, Lah JJ. LR11/SorLA expression is reduced in sporadic Alzheimer's disease but not in familial AD. J Neuropathol Exp Neurol 2006;65:866-872.
Offe K, Dodson SE, Shoemaker JT, Fritz JJ, Gearing M, Levey AI, Lah JJ. The lipoprotein receptor LR11 regulates amyloid b production and amyloid precursor protein traffic in endosomal compartments. J Neurosci 2006;26:1596-1603.
Mosaheb S, Thorpe JR, Hashemzadeh-Bonehi L, Bigio EH, Gearing M, Cairns NJ. Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion disease. Acta Neuropathol 2005;110:360-368.
Okun MS, DeLong MR, Hanfelt J, Gearing M, Levey A. Testosterone levels in an Alzheimer's-Parkinsons disease registry. Neurology 2004;62:411-413.
Choi J, Levey AI, Weintraub ST, Rees HD, Gearing M, Chin L-S, Li L. Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson's and Alzheimers diseases. J Biol Chem 2004;279:13256-13264.
Cairns NJ, Grossman M, Arnold SE, Burn DJ, Jaros E, Perry RH, Duyckaerts C, Stankoff B, Pillon B, Skullerud K, Cruz-Sanchez FF, Bigio EJ, Mackenzie IRA, Gearing M, Juncos JL, Glass JD, Yokoo H, Nakazato Y, Mosaheb S, Thorpe JR, Uryu K, Lee VM-Y, Trojanowski JQ. Clinical and neuropathologic variation in neuronal intermediate filament inclusion disease (NIFID). Neurology 2004;63:1376-1384.
Liao L, Cheng D, Wang J, Duong DM, Losik TG, Gearing M, Rees HD, Lah JJ, Levey AI, Peng J. Proteomic characterization of postmortem amyloid plaques isolated by laser capture microdissection. J Biol Chem 2004;279:37061-37068.
Cairns NJ, Zhukareva V, Uryu K, Zhang B, Bigio E, Mackenzie IRA, Gearing M, Duyckaerts C, Yokoo H, Nakazato Y, Jaros E, Perry RH, Lee VM-Y, Trojanowski JQ. a-Internexin is present in the pathological inclusions of neuronal intermediate filament inclusion disease. Am J Pathol 2004;164:2153-2161.
Salazar G, Love R, Styers ML, Werner E, Peden A, Rodriguez S, Gearing M, Wainer BH, Faundez V. AP3-dependent mechanisms control the targeting of a chloride channel (ClC3) in neuronal and non-neuronal cells. J Biol Chem 2004;279:25430-25439.
Cairns NJ, Uryu K, Bigio E, Mackenzie IRA, Gearing M, Duyckaerts C, Yokoo H, Nakazato Y, Jaros E, Perry RH, Arnold SE, Lee VM-Y, Trojanowsky JQ. a-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases. Acta Neuropathol 2004;108:213-223.
Scherzer CR, Offe K, Gearing M, Rees HD, Fang G, Heilman CJ, Schaller C, Bujo H, Levey AI, Lah JJ. Loss of ApoE receptor LR11 in Alzheimer's disease. Arch Neurol 2004;61:1200-1205.
Borges K, Gearing M, McDermott DL, Smith AB, Almonte AG, Wainer BH, Dingledine R. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Experimental Neurology 2003;182:21-34.
Gearing M, Juncos JL, Procaccio V, Gutekunst C-A, Marino EM, Gyure KA, Ono S, Santoianni R, Krawiecki NS, Wallace DC, Wainer BH. Aggregation of actin and cofilin in identical twins with juvenile-onset dystonia. Ann Neurol 2002;52:465-476.
Okun MS, Stover NP, Subramanian T, Gearing M, Wainer BH, Holder CA, Watts RL, Juncos JL, Freeman A, Evatt ML, Schuele SU, Vitek JL, DeLong MR. Complications of gamma knife surgery for Parkinson disease. Arch Neurol 2001;58:1995-2002.
Goldstein FC, Ashley AV, Gearing M, Hanfelt J, Penix L, Freedman L, Levey AI. Apolipoprotein E and age of onset of Alzheimer's disease in African American patients. Neurology 2001;57:1923-1925.
Brat DJ, Goldthwaite P, Gearing M, Wainer BH, Burger PC. Tau-associated neuropathology in ganglion cell tumors increases with patient age but is unrelated to ApoE genotype. Neuropathol Appl Neurobiol 2001;27:197-205.
Mizuno M, Gearing M, Terasawa E. The role of neuropeptide Y in the progesterone-induced luteinizing hormone-releasing hormone surge in vivo in ovariectomized female rhesus monkeys. Endocrinology 2000;141:1772-1779.
Gearing M, Lynn M, Mirra SS. Neurofibrillary pathology in Alzheimer's disease with Lewy bodies: Two subgroups. Arch Neurol 1999;56:203-208.
Mirra SS, Murrell JR, Gearing M, Spillantini MG, Goedert M, Crowther RA, Levey AI, Jones R, Green J, Shoffner JM, Wainer BH, Schmidt ML, Trojanowski JQ, Ghetti B. Tau pathology in a family with dementia and a P301L mutation in tau. J Neuropathol Exp Neurol 1999;58:335-345.
Heyman A, Fillenbaum GG, Gearing M, Mirra SS, Welsh-Bohmer KA, Peterson B, Pieper C. Comparison of Lewy body variant of Alzheimer's disease with pure Alzheimers disease. Consortium to Establish a Registry for Alzheimers Disease, part XIX. Neurology 1999;52:1839-1844.
Wolf DS, Gearing M, Snowdon DA, Mori H, Markesbery WR, Mirra SS. Progression of regional neuropathology in Alzheimer's disease and normal elderly: Findings from the Nun Study. Alzheimer Dis Assoc Disord 1999;13:226-231.
Tsuang D, Larson EB, Bowen J, McCormick W, Teri L, Nochlin D, Leverenz JB, Peskind ER, Lim A, Raskind MA, Thompson ML, Mirra SS, Gearing M, Schellenberg GD, Kukull W. The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based series. Arch Neurol 1999;56:1489-1495.
Berg L, McKeel DW Jr, Miller JP, Storandt M, Rubin EH, Morris JC, Baty J, Coats M, Norton J, Goate AM, Price JL, Gearing M, Mirra SS, Saunders AM. Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease: Relation of histologic markers to dementia severity, age, sex, and apolipoprotein E genotype. Arch Neurol 1998;55:326-335.
Mayeux R, Saunders A, Shea S, Mirra S, Evans D, Roses AD, Hyman BT, Crain B, Tang M-X, Phelps CH, and the Alzheimer's Disease Centers Consortium on Apolipoprotein E and Alzheimers Disease. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimers disease. N Engl J Med 1998;338:506-511.
Heyman A, Fillenbaum G, Welsh-Bohmer K, Gearing M, Mirra SS, Mohs R, Peterson B, Pieper C. Cerebral infarcts in patients with autopsy-proven Alzheimer's disease. CERAD, part XVIII. Neurology 1998;51:159-162.
Farrer LA, et al, and the ApoE and Alzheimer Disease Meta Analysis Consortium. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. JAMA 1997;278:1349-1356.
Welsh-Bohmer KA, Gearing M, Saunders AM, Roses AD, Mirra S. Apolipoprotein E genotypes in a neuropathological series from the Consortium to Establish a Registry for Alzheimer's Disease. Ann Neurol 1997;42:319-325.
Gearing M, Tigges J, Mori H, Mirra SS. Changes in the brains of aged orangutans. Neurobiol Aging 1997;18:139-146.
Schneider JA, Watts RL, Gearing M, Brewer RP, Mirra SS. Corticobasal degeneration: Neuropathological and clinical heterogeneity. Neurology 1997;48:959-969.
Ishii K, Tamaoka A, Mizusawa H, Shoji S, Ohtake T, Fraser PE, Takahashi H, Tsuji S, Gearing M, Mizutani T, Yamada S, Kato M, St. George-Hyslop PH, Mirra SS, Mori H. A¿1-40 but not A¿1-42 levels in cortex correlate with apolipoprotein E e4 allele dosage in sporadic Alzheimer's disease. Brain Res 1997;748:250-252.
Gearing M, Levey AI, Mirra SS. Diffuse plaques in the striatum in Alzheimer's disease (AD): Relationship to the striatal mosaic and selected neuropeptide markers. J Neuropathol Exp Neurol 1997;56:1363-1370.
Shao Y, Gearing M, Mirra SS. Astrocyte-apolipoprotein E associations in senile plaques in Alzheimer disease and vascular lesions: A regional immunohistochemical study. J Neuropathol Exp Neurol 1997;56:376-381.
Gearing M, Tigges J, Mori H, Mirra SS. A¿40 is a major form of ¿-amyloid in nonhuman primates. Neurobiol Aging 1996;17:903-908.
Gearing M, Mori H, Mirra SS. A¿ peptide length and apolipoprotein E (ApoE) genotype in Alzheimer's disease. Ann Neurol 1996;39:395-399.
Gearing M, Schneider JA, Rebeck GW, Hyman BT, Mirra SS. Alzheimer's disease with and without coexisting Parkinson's disease changes: Apolipoprotein E genotype and neuropathologic correlates. Neurology 1995;45:1985-1990.
Kim H, Gearing M, Mirra SS. Ubiquitin-positive CA2/3 neurites in hippocampus coexist with cortical Lewy bodies. Neurology 1995;45:1768-1770.
Gearing M, Schneider JA, Robbins RS, Hollister RD, Mori H, Games D, Hyman BT, Mirra SS. Regional variation in the distribution of apolipoprotein E and A¿ in Alzheimer's disease. J Neuropathol Exp Neurol 1995;54:833-841.
Schneider JA, Gearing M, Robbins RS, de l'Aune W, Mirra SS. Apolipoprotein E genotype in diverse neurodegenerative disorders. Ann Neurol 1995;38:131-135.
Gearing M, Mirra SS, Hedreen JC, Sumi SM, Hansen LA, Heyman A. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer's disease. Neurology 1995;45;461-466.
Davis PC, Gearing M, Gray L, Mirra SS, Morris JC, Edland SD, Lin T, Heyman A. The CERAD experience, Part VIII: Neuroimaging-neuropathology correlates of temporal lobe changes in Alzheimer's disease. Neurology 1995;45:178-179.
Gearing M, Olson DA, Watts RL, Mirra SS. Progressive supranuclear palsy: Neuropathological and clinical heterogeneity. Neurology 1994;44:1015-1024.
Mirra SS, Gearing M, McKeel DW Jr, Crain BJ, Hughes JP, Van Belle G, Heyman A, participating neuropathologists. Interlaboratory comparison of neuropathology assessments in Alzheimer's disease: A study of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). J Neuropathol Exp Neurol 1994;53:303-315.
Poduri A, Gearing M, Rebeck GW, Mirra SS, Tigges J, Hyman BT. Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys. Am J Pathol 1994;144:1183-1187.
Gearing M, Rebeck GW, Hyman BT, Tigges J, Mirra SS. Neuropathology and apolipoprotein E profile of aged chimpanzees: Implications for Alzheimer's disease. Proc Natl Acad Sci USA 1994;91:9382-9386.
Shoffner JM, Brown MD, Torroni A, Lott MT, Cabell MF, Mirra SS, Beal MF, Yang C-C, Gearing M, Salvo R, Watts RL, Juncos JL, Hansen LA, Crain BJ, Fayad M, Reckord CL, Wallace DC. Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients. Genomics 1993;17:171-184.
Gearing M, Wilson RW, Unger ER, Shelton ER, Chan HW, Masters CL, Beyreuther K, Mirra SS. Amyloid precursor protein (APP) in the striatum in Alzheimer's disease: An immunohistochemical study. J Neuropathol Exp Neurol 1993;52;14-21.
Gearing M, Terasawa E. Prostaglandin E2 mediates the stimulatory effect of methoxamine on in vivo luteinizing hormone releasing hormone (LHRH) release in the ovariectomized female rhesus monkey. Brain Res 1991;560:276-281.
Gearing M, Terasawa E. The alpha-1-adrenergic neuronal system is involved in the pulsatile release of luteinizing hormone-releasing hormone in the ovariectomized female rhesus monkey. Neuroendocrinology 1991;53:373-381.
Gearing M, Terasawa E. Suppression of luteinizing hormone release by the alpha1-adrenergic receptor antagonist prazosin in the ovariectomized female rhesus monkey. Am J Primatol 1991;25:23-33.
Terasawa E, Krook C, Hei DL, Gearing M, Schultz NJ, Davis GA. Norepinephrine is a possible neurotransmitter stimulating pulsatile release of luteinizing hormone releasing hormone in the rhesus monkey. Endocrinology 1988;123:1808-1816.
Gearing M, Terasawa E. Luteinizing hormone releasing hormone (LHRH) neuroterminals mapped using the push-pull perfusion method in the rhesus monkey. Brain Res Bull 1988;21:117-121.
Bruot BC, Gearing M, Musey PI, Wilson ME, Collins DC. Steroidogenesis by the immature rhesus monkey ovary in vitro. J Endocrinol Invest 1986;9:171-175.
Gearing M, Mirra SS. Neuropathology of movement disorders: An overview. In: Watts RL, Koller WC, eds. Movement Disorders: Neurologic Principles and Practice. 2nd edition. New York: McGraw-Hill, 2004:143-158.
Mirra SS, Schneider JA, Gearing M. Neuropathology of movement disorders: An overview. In: Watts RL, Koller WC, eds. Movement Disorders: Neurologic Principles and Practice. New York: McGraw-Hill, 1997:125-134.
Mirra SS, Gearing M. The neuropathology of Alzheimer's disease and related dementias. In: Morris JC, ed. Handbook of Dementing Illnesses. New York: Marcel Dekker, 1994:189-226.
Mirra SS, Gearing M. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study [letter]. JAMA 1997;278:113.
Mirra SS, Gearing M, Nash F. The neuropathological assessment of Alzheimer's disease. Neurology 1997;49(Suppl 3):S14-S16.
Gearing M, Mirra SS, Hedreen JC, Sumi SM, Hansen LA, Heyman A. AD Neuropathology: Reply. Neurology 1996;46:1186-1187.
Mirra SS, Gearing M, McKeel DW, Crain BJ, Hughes JP, van Belle G, Heyman A. Consortium to Establish a Registry for Alzheimer's Disease: Reply. J Neuropathol Exp Neurol 1995;54:131.
Mirra SS, Gearing M, Heyman A. CERAD Guide to the Neuropathological Assessment of Alzheimer's Disease and Other Dementias. Copyright CERAD, 1994.
Mirra S, Gearing M, Sumi SM, Crain B, Heyman A, CERAD neuropathologists. The neuropathological assessment of Alzheimer's disease and related dementias: The CERAD experience. In: Corain B, Iqbal K, Nicolini M, Winblad B, Wisniewski H, Zatta P, eds. Alzheimer's Disease: Advances in Clinical and Basic Research. New York: John Wiley & Sons, Ltd., 1993:207-211. Presented at the 3rd International Conference on Alzheimer's Disease and Related Disorders in Padua, Italy.