Increasing evidence suggests alterations in zinc (Zn) homeostasis may contribute to neurodegeneration observed in the pathogenesis of Alzheimer’s disease (AD). Current studies from our laboratory show there are significant alterations in proteins responsible for the transport and sequestration of Zn (ZnT proteins) that occur early in the progression of AD. Our data also suggest that alterations of ZnT proteins and the corresponding disruption of Zn balance can contribute to increased oxidative damage in AD. Our current research centers around the use of Western blot analysis, immunohistochemistry/laser confocal microscopy and genetic manipulation of neuronal cell lines to study alterations of ZnT proteins. We also use GC-MS, HPLC, cell culture techniques and transgenic animals to correlate altered ZnT levels and markers of oxidative damage including oxidized DNA adducts and neurotoxic by-products of lipid peroxidation (4-hydroxynonenal, acrolein). Additional studies include analysis of by-products of RNA oxidation in the progression of AD and evaluation of the biological impact of RNA oxidation using primary rat cortical neuron cultures.

Representative composite of cells from a subject with mild cognitive impairment (MCI) double labeled for ZnT-6 (A; green) and MC-1 (B; red), a marker of early neurofibrillary tangle formation. Figure C is a merged image. Note considerable overlap between ZnT-6 and MC-1 immunostaining. Scale bar = 50 µm.

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• M. A. Lovell*, B. C. Lynn, S. Xiong, J. F. Quinn, J. Kaye and W. R. Markesbery, “An aberrant protein complex as a biomarker of Alzheimer’s disease”, Neurology, In Press, (2008).
• M. A. Lovell* and W. R. Markesbery, “Oxidative Modification of RNA in Mild Cognitive Impairment”, Neurobiol. Dis., 29:169-175, (2008).
• M. A. Lovell* and W. R. Markesbery, “Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease”, (Invited Review) Nucleic Acids Res., 35:7497-9504, (2007).
• G. Mao, Y. Zhang, F. Yuan, B. B. Zhu, M. A. Lovell, M. P. Lee, W. R. Markesbery, L. Gu and G. M. Li, “Identification of an OGG1 Mutation Inactivating 8-oxo-guanine DNA glycosylase Activity in Patients with Alzheimer’s Disease”, Nuc. Acids Res., 35:2759-2766, (2007).
• S. Xiong, C. S. Shao, W. R. Markesbery and M. A. Lovell*, "Selenium-L-Methionine Protects Against ß-Amyloid and Iron/Hydrogen Peroxide Mediated Neuron Death," Antioxid. Redox Signal, 9:457-467, (2007).
• W. R. Markesbery and M. A. Lovell, “Lipid Peroxidation is an Early Event in the Brain in Amnestic Mild Cognitive Impairment”, (Invited Review) Archives of Neurol., 64:954-956, (2007).
• W. R. Markesbery and M.A. Lovell, “DNA Oxidation in Alzheimer’s Disease”, (Invited Review) Antioxid. Redox Signal, 8:2039-2045 (2006).
• X. Liu, M. A. Lovell and B. C. Lynn, "Detection and Quantification of Endogenous Cyclic DNA Adducts Derived from 4-Hydroxynonenal in Human Brain Tissue by Isotope Dilution Capillary Liquid Chromatography Nanoelectrospray Tandem Mass Spectrometry," Chem. Res. Toxicol., 19:710-718 (2006).
• J. L. Smith, S. Xiong, W. R. Markesbery and M. A. Lovell*, "Increased Expression of ZnT-4 and ZnT-6 in Mild Cognitive Impairment, Early and Late Stage Alzheimer's Disease," Neurosci., 140:879-888 (2006).
• J. L. Smith, S. Xiong, W. R. Markesbery and M. A. Lovell*, "4-Hydroxynonenal Disrupts Zinc Transport in Primary Rat Cortical Neurons," Neurotoxicology, 27:1-5 (2006).
• M. A. Lovell*, J. L. Smith and W. R. Markesbery, "Elevated Zinc Transporter-6 in Mild Cognitive Impairment, Alzheimer's Disease and Pick's Disease," J. Neuropathol. Exp. Neurol., 65:489-498 (2006).
• C. X. Shao, K. N. Roberts, K. M. Miller, W. R. Markebery, S. W. Scheff and M. A. Lovell*, "Oxidative Stress in Head Trauma in Aging," Free Radic. Biol. Medic., 41:77-85 (2006).
• J. Wang, W. R. Markesbery and M. A. Lovell*, "Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment," J. Neurochem., 96:825-833 (2006).
• T. I. Williams, B. C. Lynn, W. R. Markesbery and M. A. Lovell*, "Elevated 4-Hydroxynonenal and Acrolein in Mild Cognitive Impairment and Early Alzheimer's Disease," Neurobiol. Aging, 27:1094-1099, (2006).
• M. A. Lovell*, H. Geiger, G. E. Van Zant, B. C. Lynn and W. R. Markesbery, "Neural Precursor Cells from Alzheimer's Disease and Aged Control Brain," Neurobiol. Aging, 7:909-917 (2006).
• W. R. Markesbery, R. J. Kryscio, M. A. Lovell and J. D. Morrow, "Lipid Peroxidation is an Early Event in the Brain in Amnestic Mild Cognitive Impairment," Annals Neurol., 58, 730-735 (2005).
• X. Liu, M. A. Lovell and B. C. Lynn, "Development of an Isotope Dilution Capillary Liquid Chromatography Nanoelectrospray Tandem Mass Spectrometry Method for Detection and Quantification of Acrolein-Deoxyguanosine Adducts," Anal. Chem., 77, 5982-5989 (2005).
• M. A. Lovell*, J. L. Smith, S. Xiong, and W. R. Markesbery, "Alterations in Zinc Transporter Protein-1 (ZnT-1) in the Brain of Subjects with Mild Cognitive Impairment, Early, and Late-Stage Alzheimer's Disease," Neurotox. Res., 7, 265-271 (2005).
• M. A. Lovell* and W. R. Markesbery, "Ectopic Expression of Musashi-1 in Alzheimer's Disease and Pick Disease," J. Neuropathol. Exp. Neurol., 64, 1-6 (2005).
• C. D. Smith, G. R. Umberger, R. J. Kryscio, F. A. Schmitt, M. A. Lovell, L. X. Blonder and A. H. Anderson, "Longitudinal Functional Brain Alterations in Asymptomatic Women at Risk for Alzheimer's Disease," J. Neuroimaging., 15, 271-277 (2005).
• J. Q. Wang, W .R. Markesbery and M. A. Lovell*, "Increased Oxidative Nuclear and Mitochondrial DNA Damage in Alzheimer's Disease," J. Neurochem., 93, 953-962 (2005).
• T. I. Williams, M. A. Lovell and B. C. Lynn, "Analysis of Derivatized Biogenic Aldehydes by LC Tandem Mass Spectrometry," Anal. Chem., 77, 3383-3389 (2005).
• M. A. Lovell*, S. Xiong, W. R. Markesbery and B. C. Lynn, "Quantitative Proteomics Analysis of Mitochondria from Primary Neuron Cultures Treated With Amyloid Beta Peptide," Neurochem. Res., 1, 113-122 (2005).
• M. A. Lovell*, S. Xiong, C. S. Xie, P. Davies and W. R. Markesbery, "Induction of Hyperphosphoylated Tau and Paired Helical Filament Formation in Primary Rat Cortical Neuron Cultures Mediated by Glycogen Synthase Kinase-3," J. Alz. Disease., 6, 659-671 (2005).

• J. D. Robertson and M. A. Lovell, "Applications of Radioanalytical Chemistry to Alzheimer's Disease," In: Radioanalytical Methods in Interdisciplinary Research, C. A. Laue and K. L. Nash, Eds., 2004, pp. 298-306.
• M. A. Lovell and W. R. Markesbery, "Analysis of Aldehydic Markers of Lipid Peroxidation in Biological Tissues by High-Pressure Liquid Chromatography with Fluorescence Detection," In: Methods in Biological Oxidative Stress, K. Hensley, Ed., 2003, pp. 17-21.
• W. R. Markesbery, T. J. Montine and M. A. Lovell, "Oxidative Alteration in Neurodegenerative Diseases," In: The Pathogenesis of Neurodegenerative Disorders, M. P. Mattson, Ed., Humana Press, 2001, pp. 21-51.
• M. A. Lovell, W. D. Ehmann, W. R. Markesbery, S. Melethil, C. R. Swyt and P. F. Zatta, "Standardization in Biological Analyses of Aluminum: What are the Needs?" In: Research Issues in Aluminum Toxicity, R. A. Yokel and M. S. Golub, Eds., Taylor and Francis, 1997.