Sanders-Brown Faculty

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William R. Markesbery, M.D.

Director, Sanders-Brown Center on Aging, Director, Alzheimer’s Disease Center Commonwealth Chair in Aging, Professor, 2009 Zaven Khachaturian Award recipient by the Alzheimer’s Association.

Departmental Affiliation(s):

Pathology and Neurology and Sanders-Brown Center on Aging

Research Focus:

Alzheimer's disease, other dementing disorders, and central nervous system aging. His research includes studies on the pathogenesis of Alzheimer's disease, oxidative damage in Alzheimer's disease, and the neuropathology of normal aging, mild cognitive impairment, and Alzheimer's disease.

In the lab:

Huaichen Liu

Ela Patel

Sonya Anderson.

Glenda Smith

Recent Publications:

Markesbery WR, Jicha GA, Liu H, Schmitt FA.   Lewy body pathology in normal elderly subjects.  Neuropathol Exp Neurol. 2009 Jul;68(7):816-22.

Carr SA, Davis R, Spencer D, Smart M, Hudson J, Freeman S, Cooper GE, Schmitt FA, Markesbery WR, Danner D, Jicha GA. Comparison of recruitment efforts targeted at primary care physicians versus the community at large for participation in Alzheimer disease clinical trials. Alzheimer Dis Assoc Disord. 2009 Jun 30. [Epub ahead of print]

Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Santacruz K, Smith CD, Patel E, Markesbery WR.  Brains With medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease. J Neuropathol Exp Neurol. 2009 Jul;68(7):774-784.

Mortimer JA, Snowdon DA, Markesbery WR.   The effect of APOE-epsilon4 on dementia is mediated by Alzheimer neuropathology.Alzheimer Dis Assoc Disord. 2009 Apr-Jun;23(2):152-7.

Price JL, McKeel DW Jr, Buckles VD, Roe CM, Xiong C, Grundman M, Hansen LA, Petersen RC, Parisi JE, Dickson DW, Smith CD, Davis DG, Schmitt FA, Markesbery WR, Kaye J, Kurlan R, Hulette C, Kurland BF, Higdon R, Kukull W, Morris JC. Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease.  Neurobiol Aging. 2009 Jul;30(7):1026-36. Epub 2009 Apr 18.

Lyubartseva G, Smith JL, Markesbery WR, Lovell MA Alterations of zinc transporter proteins ZnT-1, ZnT-4 and ZnT-6 in preclinical Alzheimer's disease brain.  Brain Pathol. 2009 Apr 7. [Epub ahead of print]

Reed TT, Pierce WM, Markesbery WR, Butterfield DA.  Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD. Brain Res. 2009 Jun 5;1274:66-76. Epub 2009 Apr 15

Lovell MA, Xiong S, Lyubartseva G, Markesbery WR.  Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice. Free Radic Biol Med. 2009 Jun 1;46(11):1527-33. Epub 2009 Mar 19.

Nelson PT, Kryscio RJ, Abner EL, Schmitt FA, Jicha GA, Mendiondo MS, Cooper G, Smith CB, Markesbery WR.  Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer's disease and AD + DLB. J Alzheimers Dis. 2009 Jan;16(1):29-34.

Nelson PT, Braak H, Markesbery WR. Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship.  J Neuropathol Exp Neurol. 2009 Jan;68(1):1-14. Review

Nelson PT, Abner EL, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, Davis DG, Poduska JW, Patel E, Mendiondo MS, Markesbery WR Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol. 2008 Nov 19. [Epub ahead of print]

Shao C, Xiong S, Li GM, Gu L, Mao G, Markesbery WR, Lovell MA.  Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer’s disease brain. Free Radic Biol Med, 2008,45:813-819

Smith CD, Chebrolu H, Markesbery WR, Liu J.  Improved predictive model for presymptomatic mild cognitive impairment and Alzheimer’s disease. Neurol Res 2008, 30:1091-1096

Sonnen JA, Breitner JC, Lovell MA, Markesbery WR, Quinn JF, Montine TJ.  Free radical-mediated damage to brain in Alzheimer’s disease and its transgenic mouse models.  Free Radic Biol Med 2008,45:219-230

Jicha GA, Abner E, Schmitt FA, Cooper GE, Stiles N, Hamon R, Carr S, Smith, CD, Markesbery WR.  Clinical features of mild cognitive impairment differ in the research and tertiary clinic settings. Dement Geriatr Cogn Disord 2008 26:187-192.

Lovell MA, Lynn BC, Xiong S, Quinn JF, Kaye J, Markesbery WR.  An aberrant protein complex in CSF as a biomarker of Alzheimer’s disease.  Neurology 2008, 70: 2212-2218

Lovell MA, Markesbery WR.  Oxidatively modified RNA in mild cognitive impairment. Neurobiol Dis 2008 29: 169-175

Jicha GA, Schmitt FA, Abner E, Nelson PT, Cooper GE, Smith CD, Markesbery WR.  Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease. Neurobiol Aging. 2008, Nov 19. [Epub ahead of print]

Nelson PT, Abner EL, Scheff SW, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, Patel E, Markesbery WR. Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment. Neurosci Lett. 2009 Feb 6;450(3):336-9. Epub 2008 Nov 8.

Lovell MA, Markesbery WR. Oxidatively modified RNA in mild cognitive impairment. Neurobiol Dis 29: 169-175, 2008.

Nelson PT, Abner EL, Scheff SW, Schmitt FA, Kryscio RJ, Jicha GA, Smith CD, Patel E, Markesbery WR. Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment. Neurosci Lett. 2009 Feb 6;450(3):336-9. Epub 2008 Nov 8.

Markesbery WR, Lovell MA.  Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. Arch Neurol 2007, 64: 954-956

Lovell MA, Markesbery WR.  Oxidative damage in mild cognitive impairment and early Alzheimer's disease. J Neurosci Res 2007, 85: 3036-3040

Butterfield DA, Reed TT, Perluigi M, De Marco C, Coccia R, Keller JN, Markesbery WR, Sultana R. Elevated levels of 3-nitrotyrosine in brain from subjects with amnestic mild cognitive impairment: implications for the role of nitration in the progression of Alzheimer's disease. Brain Res 1148: 243-248, 2007.

Launer LJ, Petrovitch H, Ross GW, Markesbery W, White LR. AD brain pathology: Vascular origins? Results from the HAAS autopsy study. Neurobiol Aging: Epub ahead of print, 2007.

Lovell MA, Markesbery WR. Oxidative damage in mild cognitive impairment and early Alzheimer's disease. J Neurosci Res 85: 3036-3040, 2007.

Lovell MA, Markesbery WR. Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's disease. Nucleic Acids Res 35: 7497-7504, 2007.

Mao G, Pan X, Zhu BB, Zhang Y, Yuan F, Huang J, Lovell MA, Lee MP, Markesbery WR, Li GM, Gu L. Identification and characterization of OGG1 mutations in patients with Alzheimer's disease. Nucleic Acids Res 35: 2759-2766, 2007.

Markesbery WR, Lovell MA. Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. Arch Neurol 64: 954-956, 2007.

Murphy MP, Beckett TL, Ding Q, Patel E, Markesbery WR, St Clair DK, LeVine H, 3rd, Keller JN. Abeta solubility and deposition during AD progression and in APPxPS-1 knock-in mice. Neurobiol Dis 27: 301-311, 2007.

Nelson PT, Jicha GA, Schmitt FA, Liu H, Davis DG, Mendiondo MS, Abner EL, Markesbery WR. Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severity. J Neuropathol Exp Neurol 66: 1136-1146, 2007.

Neumann M, Mackenzie IR, Cairns NJ, Boyer PJ, Markesbery WR, Smith CD, Taylor JP, Kretzschmar HA, Kimonis VE, Forman MS. TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J Neuropathol Exp Neurol 66: 152-157, 2007.

Petrovitch H, Ross GW, He Q, Uyehara-Lock J, Markesbery W, Davis D, Nelson J, Masaki K, Launer L, White LR. Characterization of Japanese-American men with a single neocortical AD lesion type. Neurobiol Aging: Epub ahead of print, 2007.

Smith CD, Chebrolu H, Wekstein DR, Schmitt FA, Jicha GA, Cooper G, Markesbery WR. Brain structural alterations before mild cognitive impairment. Neurology 68: 1268-1273, 2007.

Smith CD, Chebrolu H, Wekstein DR, Schmitt FA, Markesbery WR. Age and gender effects on human brain anatomy: a voxel-based morphometric study in healthy elderly. Neurobiol Aging 28: 1075-1087, 2007.

Tyas SL, Snowdon DA, Desrosiers MF, Riley KP, Markesbery WR. Healthy ageing in the Nun Study: definition and neuropathologic correlates. Age Ageing 36: 650-655, 2007.

Weissman L, Jo DG, Sorensen MM, de Souza-Pinto NC, Markesbery WR, Mattson MP, Bohr VA. Defective DNA base excision repair in brain from individuals with Alzheimer's disease and amnestic mild cognitive impairment. Nucleic Acids Res 35: 5545-5555, 2007.

Xiong S, Markesbery WR, Shao C, Lovell MA. Seleno-L-methionine protects against beta-amyloid and iron/hydrogen peroxide-mediated neuron death. Antioxid Redox Signal 9: 457-467, 2007.

Youn H, Jeoung M, Koo Y, Ji H, Markesbery WR, Ji I, Ji TH. Kalirin is under-expressed in Alzheimer's disease hippocampus. J Alzheimers Dis 11: 385-397, 2007.

Youn H, Ji I, Ji HP, Markesbery WR, Ji TH. Under-expression of Kalirin-7 Increases iNOS Activity in Cultured Cells and Correlates to Elevated iNOS Activity in Alzheimer's Disease Hippocampus. J Alzheimers Dis 12: 271-281, 2007.

Ding Q, Markesbery WR, Cecarini V, Keller JN.  Decreased RNA, and increased RNA oxidation, in ribosomes from early Alzheimer's disease. Neurochem Res 2006, 31: 705-710

Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR.  Neuropathologic substrate of mild cognitive impairment. Arch Neurol 2006, 63: 38-46

Markesbery WR, Kryscio RJ, Lovell MA, Morrow JD.  Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment. Ann Neurol 2005, 58: 730-735