William Markesbery

Summary

Affiliation: University of Kentucky
Country: USA

Publications

  1. pmc Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain
    Karrie E Grear
    Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
    Mol Neurodegener 4:46. 2009
  2. ncbi request reprint Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment
    William R Markesbery
    Department of Neurology, University of Kentucky, Lexington, KY 40536 0230, USA
    Arch Neurol 64:954-6. 2007
  3. ncbi request reprint DNA oxidation in Alzheimer's disease
    William R Markesbery
    Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    Antioxid Redox Signal 8:2039-45. 2006
  4. pmc Lewy body pathology in normal elderly subjects
    William R Markesbery
    Alzheimer s Disease Center and the Sanders Brown Center on Aging, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    J Neuropathol Exp Neurol 68:816-22. 2009
  5. ncbi request reprint Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment
    William R Markesbery
    Alzheimer s Disease Research Center, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
    Ann Neurol 58:730-5. 2005
  6. ncbi request reprint Neuropathologic substrate of mild cognitive impairment
    William R Markesbery
    Alzheimer s Disease Center, University of Kentucky, Lexington, KY 40536 0230, USA
    Arch Neurol 63:38-46. 2006
  7. pmc Neuropathologic alterations in mild cognitive impairment: a review
    William R Markesbery
    Department of Pathology and Laboratory Medicine, Sanders Brown Center on Aging, and Alzheimer s Disease Center, University of Kentucky College of Medicine, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    J Alzheimers Dis 19:221-8. 2010
  8. ncbi request reprint Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for
    Hafiz Mohmmad Abdul
    Department of Chemistry and Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506, USA
    J Neurochem 96:1322-35. 2006
  9. pmc Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease
    Muthuswamy Anantharaman
    Graduate Center for Toxicology, University of Kentucky, Lexington 40536 0305, USA
    Am J Pathol 168:1608-18. 2006
  10. ncbi request reprint Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1
    Alessandra Castegna
    Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington 40506 0055, USA
    Free Radic Biol Med 33:562-71. 2002

Research Grants

  1. OXIDATIVE STRESS IN ALZHEIMER'S DISEASE
    William Markesbery; Fiscal Year: 2006
  2. PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUM
    William Markesbery; Fiscal Year: 2007
  3. PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUM
    William Markesbery; Fiscal Year: 2006
  4. ALZHEIMER'S DISEASE RESEARCH CENTER
    William Markesbery; Fiscal Year: 2005
  5. Prevention of Alzheimer's Diseae by Vitamin E and Selenium
    William Markesbery; Fiscal Year: 2009

Detail Information

Publications85

  1. pmc Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain
    Karrie E Grear
    Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
    Mol Neurodegener 4:46. 2009
    ..abstract:..
  2. ncbi request reprint Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment
    William R Markesbery
    Department of Neurology, University of Kentucky, Lexington, KY 40536 0230, USA
    Arch Neurol 64:954-6. 2007
    ..These studies establish oxidative damage as an early event in the pathogenesis of Alzheimer disease that can serve as a therapeutic target to slow the progression or perhaps the onset of the disease...
  3. ncbi request reprint DNA oxidation in Alzheimer's disease
    William R Markesbery
    Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    Antioxid Redox Signal 8:2039-45. 2006
    ....
  4. pmc Lewy body pathology in normal elderly subjects
    William R Markesbery
    Alzheimer s Disease Center and the Sanders Brown Center on Aging, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA
    J Neuropathol Exp Neurol 68:816-22. 2009
    ..Overall, our findings support the concept that incidental Lewy body disease most likely represents preclinical or presymptomatic Parkinson disease, Parkinson disease with dementia, or dementia with Lewy bodies...
  5. ncbi request reprint Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment
    William R Markesbery
    Alzheimer s Disease Research Center, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
    Ann Neurol 58:730-5. 2005
    ..Our data indicate that lipid peroxidation is present in the brain of MCI patients and suggest that oxidative damage may play a role in the pathogenesis of AD...
  6. ncbi request reprint Neuropathologic substrate of mild cognitive impairment
    William R Markesbery
    Alzheimer s Disease Center, University of Kentucky, Lexington, KY 40536 0230, USA
    Arch Neurol 63:38-46. 2006
    ..To define the neuropathologic findings in amnestic mild cognitive impairment (MCI) and early Alzheimer disease (EAD)...
  7. pmc Neuropathologic alterations in mild cognitive impairment: a review
    William R Markesbery
    Department of Pathology and Laboratory Medicine, Sanders Brown Center on Aging, and Alzheimer s Disease Center, University of Kentucky College of Medicine, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    J Alzheimers Dis 19:221-8. 2010
    ..In early AD, the phase following MCI, the significant change is an increase in neurofibrillary tangles in the neocortex that correlates with an increase in Braak score and the observed clinical progression...
  8. ncbi request reprint Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for
    Hafiz Mohmmad Abdul
    Department of Chemistry and Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506, USA
    J Neurochem 96:1322-35. 2006
    ..The results are consonant with the hypothesis that Abeta(1-42)-associated oxidative stress and increased vulnerability to oxidative stress may contribute significantly to neuronal apoptosis and death in familial early onset AD...
  9. pmc Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer's disease
    Muthuswamy Anantharaman
    Graduate Center for Toxicology, University of Kentucky, Lexington 40536 0305, USA
    Am J Pathol 168:1608-18. 2006
    ..The compromised activity of MnSOD, a primary antioxidant enzyme protecting mitochondria, may explain mitochondrial dysfunction and provide the missing link between Abeta-induced oxidative stress and Alzheimer's disease...
  10. ncbi request reprint Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1
    Alessandra Castegna
    Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington 40506 0055, USA
    Free Radic Biol Med 33:562-71. 2002
    ..Proteomics offers a rapid means of identifying oxidatively modified proteins in aging and age-related neurodegenerative disorders without the limitations of the immunochemical detection method...
  11. ncbi request reprint Identification of nitrated proteins in Alzheimer's disease brain using a redox proteomics approach
    Rukhsana Sultana
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Neurobiol Dis 22:76-87. 2006
    ..Our results are discussed in context of the role of oxidative stress as one of the important mechanisms of neurodegeneration in AD...
  12. pmc Age-related loss of phospholipid asymmetry in APP(NLh)/APP(NLh) x PS-1(P264L)/PS-1(P264L) human double mutant knock-in mice: relevance to Alzheimer disease
    Miranda L Bader Lange
    Department of Chemistry, University of Kentucky, Lexington, KY 40506 0055, USA
    Neurobiol Dis 38:104-15. 2010
    ..These results are discussed with relevance to loss of lipid asymmetry and consequent neurotoxicity in brain of subjects with Alzheimer disease...
  13. ncbi request reprint Oxidative modification and down-regulation of Pin1 in Alzheimer's disease hippocampus: A redox proteomics analysis
    Rukhsana Sultana
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Neurobiol Aging 27:918-25. 2006
    ..Taken together, these results provide evidence supporting a direct link between oxidative damage to neuronal Pin1 and the pathobiology of AD...
  14. ncbi request reprint Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun Study
    Kathryn P Riley
    Department of Preventive Medicine, University of Kentucky, Lexington, KY 40536, USA
    Neurobiol Aging 26:341-7. 2005
    ..Low idea density also was significantly associated with lower brain weight, higher degree of cerebral atrophy, more severe neurofibrillary pathology, and the likelihood of meeting neuropathologic criteria for Alzheimer's disease...
  15. pmc Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease
    Joseph L Price
    Department of Anatomy and Neurobiology, Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA
    Neurobiol Aging 30:1026-36. 2009
    ..To determine the frequency and possible cognitive effect of histological Alzheimer's disease (AD) in autopsied older nondemented individuals...
  16. pmc Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in mice
    Christa M Studzinski
    Sanders Brown Center on Aging, University of Kentucky, Lexington, USA
    J Neurochem 108:860-6. 2009
    ..These data have important implications for understanding how WD may potentially contribute to brain dysfunction and the development of neurodegenerative disorders such as Alzheimer's disease...
  17. pmc Oxidative damage in brain from human mutant APP/PS-1 double knock-in mice as a function of age
    Hafiz Mohmmad Abdul
    Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington, KY 40506 0055, USA
    Free Radic Biol Med 45:1420-5. 2008
    ..These results are discussed with reference to the importance of Abeta42-associated oxidative stress in the pathogenesis of AD...
  18. doi request reprint Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease
    Tanea Reed
    Department of Chemistry, University of Kentucky, Lexington, KY 40506 0055, USA
    Neurobiol Dis 30:107-20. 2008
    ..We suggest that impairment of target proteins through the production of HNE adducts leads to protein dysfunction and eventually neuronal death, thus contributing to the biological events that may lead MCI patients to progress to AD...
  19. ncbi request reprint Proteomic identification of nitrated proteins in Alzheimer's disease brain
    Alessandra Castegna
    Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506 0055, USA
    J Neurochem 85:1394-401. 2003
    ....
  20. ncbi request reprint Redox proteomics identification of oxidized proteins in Alzheimer's disease hippocampus and cerebellum: an approach to understand pathological and biochemical alterations in AD
    Rukhsana Sultana
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Neurobiol Aging 27:1564-76. 2006
    ..The identification of common oxidized proteins in different brain regions of AD brain suggests a potential role for these oxidized proteins and thereby oxidative stress in the pathogenesis of Alzheimer's disease...
  21. ncbi request reprint Seleno-L-methionine protects against beta-amyloid and iron/hydrogen peroxide-mediated neuron death
    Shuling Xiong
    Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536, USA
    Antioxid Redox Signal 9:457-67. 2007
    ....
  22. pmc Alterations of zinc transporter proteins ZnT-1, ZnT-4 and ZnT-6 in preclinical Alzheimer's disease brain
    Ganna Lyubartseva
    Department of Chemistry, Sanders Brown Center on Aging, Lexington, KY 40536, USA
    Brain Pathol 20:343-50. 2010
    ..Overall, our results suggest that alterations in Zn transport proteins may contribute to the pathology observed in PCAD subjects before onset of clinical symptoms...
  23. ncbi request reprint Oxidative stress in head trauma in aging
    Changxing Shao
    Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
    Free Radic Biol Med 41:77-85. 2006
    ..Glutathione reductase activity also showed an age-dependent decrease. Overall, our data show increased levels of oxidative damage, diminished antioxidant capacities, and increased tissue loss in TBI in aging...
  24. pmc Preclinical Alzheimer disease: brain oxidative stress, Abeta peptide and proteomics
    Christopher D Aluise
    Department of Chemistry, Center of Membrane Sciences, and Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA
    Neurobiol Dis 39:221-8. 2010
    ..Our analyses may reveal processes involved in a period of protection from neurodegeneration that mimic the clinical phenotype of PCAD...
  25. doi request reprint Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of AD
    Tanea T Reed
    Department of Chemistry, Center of Membrane Sciences, and Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA
    Brain Res 1274:66-76. 2009
    ....
  26. ncbi request reprint Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study
    Kathryn P Riley
    Sanders Brown Center on Aging, Department of Preventive Medicine, University of Kentucky, Lexington, KY 40536, USA
    Ann Neurol 51:567-77. 2002
    ..Additional studies are needed to help explain the variability in neuropathologic findings seen in individuals whose cognitive performance falls between intact function and dementia...
  27. ncbi request reprint Ribosome dysfunction is an early event in Alzheimer's disease
    Qunxing Ding
    Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    J Neurosci 25:9171-5. 2005
    ....
  28. ncbi request reprint Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment
    Jianquan Wang
    Department of Chemistry, University of Kentucky, Lexington, KY 40536 0230, USA
    J Neurochem 96:825-32. 2006
    ..These results suggest that oxidative damage to nuclear and mitochondrial DNA occurs in the earliest detectable phase of AD and may play a meaningful role in the pathogenesis of this disease...
  29. ncbi request reprint Proteasome inhibition increases DNA and RNA oxidation in astrocyte and neuron cultures
    Qunxing Ding
    Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA
    J Neurochem 91:1211-8. 2004
    ....
  30. ncbi request reprint Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71
    Alessandra Castegna
    Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506, USA
    J Neurochem 82:1524-32. 2002
    ..These results are discussed with reference to potential involvement of these oxidatively modified proteins in neurodegeneration in AD brain...
  31. pmc Omega-3 fatty acids: potential role in the management of early Alzheimer's disease
    Gregory A Jicha
    University of Kentucky, Alzheimer s Disease Center and the Sanders Brown Center on Aging University of Kentucky College of Medicine, Lexington, KY 40536 0230, USA
    Clin Interv Aging 5:45-61. 2010
    ..However, these trials produced intriguing data suggesting that the beneficial effects of omega-3 fatty acid supplementation may depend on the stage of disease, other dietary mediators, and apolipoprotein E status...
  32. pmc Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severity
    Peter T Nelson
    Department of Pathology and Division of Neuropathology, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    J Neuropathol Exp Neurol 66:1136-46. 2007
    ..Our data show that there are many important contributory causes to cognitive decline in older persons. However, NFTs and NPs should not be dismissed as irrelevant in AD based on clinicopathologic correlation...
  33. pmc Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship
    Peter T Nelson
    Department of Pathology and Division of Neuropathology, University of Kentucky Medical Center, Sanders Brown Center on Aging, Lexington, KY 40536 0230, USA
    J Neuropathol Exp Neurol 68:1-14. 2009
    ..We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment...
  34. pmc Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's disease
    Mark A Lovell
    Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
    Nucleic Acids Res 35:7497-504. 2007
    ....
  35. ncbi request reprint Abeta solubility and deposition during AD progression and in APPxPS-1 knock-in mice
    M Paul Murphy
    Department of Molecular and Cellular Biochemistry, Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    Neurobiol Dis 27:301-11. 2007
    ..These data suggest that distinct changes in Abeta occur throughout the progression of AD, and that elevations in Abeta42 occur at an early, clinically defined stage...
  36. pmc Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brain
    Changxing Shao
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Free Radic Biol Med 45:813-9. 2008
    ..Overall, our results suggest that decreased OGG1 activity occurs early in the progression of AD, possibly mediated by 4-hydroxynonenal inactivation and may contribute to elevated 8-OHdG in the brain in MCI and LAD...
  37. pmc Quantitative changes in the mitochondrial proteome from subjects with mild cognitive impairment, early stage, and late stage Alzheimer's disease
    Bert C Lynn
    Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA
    J Alzheimers Dis 19:325-39. 2010
    ..Comparison of protein changes throughout the progression of AD suggests the most pronounced changes occur in early AD mitochondria...
  38. pmc Association between male gender and cortical Lewy body pathology in large autopsy series
    Peter T Nelson
    Division of Neuropathology, Department of Pathology, Sanders Brown Center on Aging, University of Kentucky, Rm 311, Sanders Brown Building, 800 S Limestone, Lexington, KY 40536 0230, USA
    J Neurol 257:1875-81. 2010
    ..05 for both). Males are far more likely than females to die with neocortical LB pathology. This phenomenon may help guide medical practice including clinical trial study design...
  39. pmc Low sensitivity in clinical diagnoses of dementia with Lewy bodies
    Peter T Nelson
    Division of Neuropathology, Department of Pathology, University of Kentucky Medical Center, University of Kentucky, Rm 311, Sanders Brown Building, 800 S Limestone, Lexington, KY 40536 0230, USA
    J Neurol 257:359-66. 2010
    ..Our data suggest that further work is needed to refine our ability to identify specific aging-related brain disease mechanisms, especially in DLB...
  40. pmc Comparison of recruitment efforts targeted at primary care physicians versus the community at large for participation in Alzheimer disease clinical trials
    Sarah A Carr
    Department of Neurology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
    Alzheimer Dis Assoc Disord 24:165-70. 2010
    ..Our results suggest that outreach efforts directed at the potential study subject/caregiver are not only cost-effective but are able to easily accomplish the desired result of direct recruitment into clinical research studies...
  41. pmc 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
    Peter T Nelson
    Department of Pathology and Division of Neuropathology, Univerisity of Kentucky, Lexington, Kentucky 40536 0230, USA
    J Neuropathol Exp Neurol 68:774-84. 2009
    ..We conclude that NFT+/NP- cases comprise approximately 5% of aged individuals in multiple data sets; these cases are not necessarily within the spectrum of AD...
  42. pmc Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice
    Mark A Lovell
    Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
    Free Radic Biol Med 46:1527-33. 2009
    ..5). Overall, these data suggest that organic Se can reduce Abeta burden and minimize DNA and RNA oxidation and support a role for it as a potential therapeutic agent in neurologic disorders with increased oxidative stress...
  43. pmc Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer's disease and AD + DLB
    Peter T Nelson
    Department of Pathology, University of Kentucky Medical Center, University of Kentucky, Lexington, KY, USA
    J Alzheimers Dis 16:29-34. 2009
    ..In both diseases, treatment with acetylcholinesterase inhibitors was associated with a slower rate of cognitive decline...
  44. pmc Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment
    Peter T Nelson
    Department of Pathology and Division of Neuropathology, University of Kentucky Medical Center, Sanders Brown Center on Aging and Alzheimer s Disease Center, University of Kentucky, Lexington, KY 40536, USA
    Neurosci Lett 450:336-9. 2009
    ..Our results are not consistent with the idea that the precuneus is involved in a special way with plaques or tangles relative to other areas of neocortex...
  45. pmc Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons
    Peter T Nelson
    Department of Pathology and Division of Neuropathology, University of Kentucky Medical Center, Sanders Brown Center on Aging and Alzheimer s Disease Center, University of Kentucky, Lexington, KY, USA
    Brain Pathol 20:66-79. 2010
    ..There was no support for independent association between CILA severity and most evaluated indices including diffuse plaques, argyrophilic grains, heart disease, education level, apolipoprotein E alleles or diabetes...
  46. pmc Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobule
    Tanea T Reed
    Department of Chemistry, University of Kentucky, Lexington, KY 40506 0055, USA
    J Cell Mol Med 13:2019-29. 2009
    ..These results are discussed in terms of potential involvement in the progression of this dementing disorder...
  47. ncbi request reprint Quantitative proteomic analysis of mitochondria from primary neuron cultures treated with amyloid beta peptide
    Mark A Lovell
    Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
    Neurochem Res 30:113-22. 2005
    ..Elevations of proteins associated with energy production suggest that cells undergoing Abeta-mediated apoptosis increase synthesis of proteins essential for ATP production and efflux in an attempt to maintain metabolic function...
  48. ncbi request reprint Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease
    D Allan Butterfield
    Department of Chemistry, University of Kentucky, Lexington, KY 40506 0055, USA
    Neurobiol Dis 22:223-32. 2006
    ..The current study provides a framework for future studies on the development of AD from MCI relevant to oxidative stress...
  49. ncbi request reprint 3alpha,5alpha-THP: a potential plasma neurosteroid biomarker in Alzheimer's disease and perhaps non-Alzheimer's dementia
    Charles D Smith
    Department of Neurology, University of Kentucky Medical Center, Lexington, KY 40536 0098, USA
    Psychopharmacology (Berl) 186:481-5. 2006
    ..Recent literature suggests that neurosteroid metabolism may be altered in Alzheimer's disease (AD)...
  50. ncbi request reprint Ectopic expression of Musashi-1 in Alzheimer disease and Pick disease
    Mark A Lovell
    Department of Chemistry, Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA
    J Neuropathol Exp Neurol 64:675-80. 2005
    ..The presence of Msi-1 in a significant percentage of neurons containing cytoplasmic inclusions in 2 different neurodegenerative diseases suggests that it may play a role in the pathogenesis of these lesions...
  51. ncbi request reprint Biophysical and biochemical characterization of the intrinsic fluorescence from neurofibrillary tangles
    Guoying Bing
    Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536 0098, USA
    Neurobiol Aging 27:823-30. 2006
    ..The induced fluorophore, thus, has unique properties, and its generation likely depends on the particular conformation of paired helical filaments, which may in turn depend on tau hyperphosphorylation...
  52. ncbi request reprint Induction of hyperphosphorylated tau in primary rat cortical neuron cultures mediated by oxidative stress and glycogen synthase kinase-3
    Mark A Lovell
    Sanders Brown Center on Aging and Alzheimer s Disease Research Center, 101 Sanders Brown Bldg, University of Kentucky, Lexington, KY 40536 0230, USA
    J Alzheimers Dis 6:659-71; discussion 673-81. 2004
    ..Together these data suggest a culture model of hyperphosphorylated tau that implicates increased GSK-3 activity...
  53. ncbi request reprint Designing a large prevention trial: statistical issues
    Richard J Kryscio
    Department of Statistics, University of Kentucky, Lexington 40536 0230, USA
    Stat Med 23:285-96. 2004
    ..This framework is illustrated by PREADVISE, a recently initiated large add-on prevention trial investigating the use of anti-oxidants for preventing AD among men enrolled in a even larger prostate cancer prevention study, SELECT...
  54. ncbi request reprint Wilms' tumor suppressor (WT1) is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer's disease
    Mark A Lovell
    Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
    Brain Res 983:84-96. 2003
    ..Together, these data suggest a role for WT1 in the neurodegeneration observed in AD brain...
  55. ncbi request reprint Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid
    Mark A Lovell
    Sanders Brown Center on Aging, University of Kentucky, 800 S Limestone St, Lexington, KY 40536 0230, USA
    J Alzheimers Dis 5:229-39. 2003
    ....
  56. pmc Human cerebral neuropathology of Type 2 diabetes mellitus
    Peter T Nelson
    Department of Pathology, Division of Neuropathology, University of Kentucky Medical Center, Sanders Brown Center on Aging and Alzheimer s Disease Center, University of Kentucky, Lexington, KY 40536 0230, USA
    Biochim Biophys Acta 1792:454-69. 2009
    ..These preliminary, correlative, and descriptive studies may help develop new hypotheses about CNDM2. We conclude that more work should be performed on human material in the context of CNDM2...
  57. ncbi request reprint Association of HFE mutations with neurodegeneration and oxidative stress in Alzheimer's disease and correlation with APOE
    Joseph F Pulliam
    Department of Pathology, University of Kentucky, Lexington, Kentucky 40536, USA
    Am J Med Genet B Neuropsychiatr Genet 119:48-53. 2003
    ....
  58. ncbi request reprint Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development
    Avindra Nath
    Department of Neurology, University of Kentucky, Lexington, KY 40536, USA
    Neuromolecular Med 3:29-39. 2003
    ..Our data suggest that a humoral immune response to Abeta in AD patients may promote neuronal degeneration, a process with important implications for the future of vaccine-based therapies for AD...
  59. ncbi request reprint Alzheimer's disease and head circumference
    Patricio S Espinosa
    Department of Neurology, Sanders Brown Center on Aging University of Kentucky Alzheimer s Disease Research Center, Lexington, KY 40536 0284, USA
    J Alzheimers Dis 9:77-80. 2006
    ..Larger head circumference (HC) may therefore be associated with later detection and diagnosis of AD. We investigated HC in nondemented individuals and AD patients using cross-sectional and prospective analyses...
  60. ncbi request reprint Elevated zinc transporter-6 in mild cognitive impairment, Alzheimer disease, and pick disease
    Mark A Lovell
    Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA
    J Neuropathol Exp Neurol 65:489-98. 2006
    ..Increased ZnT-6 immunostaining in neurons containing cytoplasmic inclusions in MCI, AD, and PD suggests a role for ZnT-6 in the pathogenesis of these lesions...
  61. ncbi request reprint Age and gender effects on human brain anatomy: a voxel-based morphometric study in healthy elderly
    Charles D Smith
    Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40536 0098, United States
    Neurobiol Aging 28:1075-87. 2007
    ..We did not observe significant gender effects. These findings establish a baseline for comparison with pathologic changes in human brain volume between ages 58 and 95 years...
  62. ncbi request reprint Amyloid beta peptide, 4-hydroxynonenal and apoptosis
    Mark A Lovell
    Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
    Curr Alzheimer Res 3:359-64. 2006
    ..This review discusses current evidence supporting the role of oxidative stress/damage mediated apoptosis in in vitro models of neurodegeneration...
  63. doi request reprint Small head circumference is associated with less education in persons at risk for Alzheimer disease in later life
    James A Mortimer
    Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL 33612 3805, USA
    Alzheimer Dis Assoc Disord 22:249-54. 2008
    ..These findings suggest that small HC limits educational attainment only among individuals who have greater risk of AD owing to their APOE genotype or who are destined to develop this illness later in life...
  64. ncbi request reprint Head circumference, education and risk of dementia: findings from the Nun Study
    James A Mortimer
    Institute on Aging, University of South Florida, Tampa, FL 33612 3899, USA
    J Clin Exp Neuropsychol 25:671-9. 2003
    ..The findings suggest that higher education and larger head size, alone or in combination, may reduce the risk of expressing dementia in late life...
  65. pmc Healthy ageing in the Nun Study: definition and neuropathologic correlates
    Suzanne L Tyas
    Department of Health Studies and Gerontology, University of Waterloo, Waterloo, Ontario, Canada
    Age Ageing 36:650-5. 2007
    ..Although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined...
  66. ncbi request reprint Kalirin is under-expressed in Alzheimer's disease hippocampus
    HyeSook Youn
    Department of Chemistry, University of Kentucky, Lexington, KY 40515 0055, USA
    J Alzheimers Dis 11:385-97. 2007
    ..Furthermore, housekeeping genes such as ribosomal protein genes are not affected by AD. These results provide new insights into the biochemistry of AD...
  67. pmc Defective DNA base excision repair in brain from individuals with Alzheimer's disease and amnestic mild cognitive impairment
    Lior Weissman
    Laboratories of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA
    Nucleic Acids Res 35:5545-55. 2007
    ..The results support the hypothesis that defective BER may play an important role in the progression of AD...
  68. ncbi request reprint TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations
    Manuela Neumann
    Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany
    J Neuropathol Exp Neurol 66:152-7. 2007
    ..TDP-43 is a common pathologic substrate linking a variety of distinct patterns of FTLD-U pathology caused by different genetic alterations...
  69. ncbi request reprint Oxidative damage in mild cognitive impairment and early Alzheimer's disease
    Mark A Lovell
    Department of Chemistry, University of Kentucky, Lexington, Kentucky, USA
    J Neurosci Res 85:3036-40. 2007
    ..Because oxidative damage begins early in the progress of the disease, it represents a potential therapeutic target for slowing the onset and progression of AD...
  70. ncbi request reprint Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants
    Lon White
    Kuakini Medical Center, 846 S Hotel Street, Honolulu, HI 96813, USA
    Ann N Y Acad Sci 977:9-23. 2002
    ..The cerebrovascular lesion type most essentially and inclusively related to dementia was multiple microinfarction...
  71. ncbi request reprint Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentration
    Casey N Bassett
    Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
    J Alzheimers Dis 4:19-30. 2002
    ....
  72. ncbi request reprint The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brain
    Kelly S Williamson
    Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA
    Nitric Oxide 6:221-7. 2002
    ..The findings are discussed in reference to the neuroinflammatory hypothesis of AD and the possible role of gamma-tocopherol as a major lipid-phase scavenger of reactive nitrogen species...
  73. ncbi request reprint 4-Hydroxynonenal oxidatively modifies histones: implications for Alzheimer's disease
    Jennifer Drake
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Neurosci Lett 356:155-8. 2004
    ..Conceivably, altered DNA-histone interactions, subsequent to oxidative modification of histones by the lipid peroxidation product HNE, may contribute to the vulnerability of DNA to oxidation in AD brain...
  74. ncbi request reprint F2-isoprostanes in Alzheimer and other neurodegenerative diseases
    Thomas J Montine
    Department of Pathology, University of Washington, Seattle, WA 98104, USA
    Antioxid Redox Signal 7:269-75. 2005
    ..These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F2-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD...
  75. pmc Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenal
    Sung Chun Tang
    Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224, USA
    Exp Neurol 213:114-21. 2008
    ..Our findings suggest that TLR4 signaling increases the vulnerability of neurons to Abeta and oxidative stress in AD, and identify TLR4 as a potential therapeutic target for AD...
  76. ncbi request reprint Decreased RNA, and increased RNA oxidation, in ribosomes from early Alzheimer's disease
    Qunxing Ding
    Anatomy and Neurobiology, University of Kentucky, 205 Sanders Brown Center on Aging, Lexington, KY 40536 0230, USA
    Neurochem Res 31:705-10. 2006
    ..Together, these data strongly suggest a role for RNA alterations within the ribosome as a mediator of decreased protein synthesis in both MCI and AD...
  77. pmc Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models
    Joshua A Sonnen
    Department of Pathology and of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
    Free Radic Biol Med 45:219-30. 2008
    ..Future efforts in preclinical models and ultimately clinical trials are needed to define optimally effective agents and combinations, doses, and timing to suppress safely this facet of AD...
  78. ncbi request reprint Under-expression of Kalirin-7 Increases iNOS activity in cultured cells and correlates to elevated iNOS activity in Alzheimer's disease hippocampus
    HyeSook Youn
    Department of Chemistry, University of Kentucky, Lexington, KY 40506 0055, USA
    J Alzheimers Dis 12:271-81. 2007
    ..These observations suggest that the under-expression of Kalirin-7 in AD hippocampus correlates to the elevated iNOS activity...
  79. ncbi request reprint Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease
    Taufika Islam Williams
    Department of Chemistry, University of Kentucky, 135 Sanders Brown Center on Aging, Lexington, KY 40506, USA
    Neurobiol Aging 27:1094-9. 2006
    ..We did not observe any statistically significant differences between MCI and EAD specimens. These results suggest that lipid peroxidation occurs early in the pathogenesis of AD...
  80. ncbi request reprint Isolation of neural precursor cells from Alzheimer's disease and aged control postmortem brain
    Mark A Lovell
    Sanders Brown Center on Aging and Alzheimer s Disease Research Center, 800 S Limestone St, 101 Sanders Brown Bldg, University of Kentucky, Lexington, KY 40536 0230, USA
    Neurobiol Aging 27:909-17. 2006
    ..These results raise the possibility of stimulation of inherent precursor cells of aged individuals or AD patients to replace neurons lost in aging and/or neurodegeneration...
  81. ncbi request reprint Association of olfactory dysfunction with incidental Lewy bodies
    G Webster Ross
    Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii, USA
    Mov Disord 21:2062-7. 2006
    ..0 (P = 0.02). Olfactory dysfunction is associated with ILB. If incidental Lewy bodies represent presymptomatic stage of PD, olfactory testing may be a useful screening tool to identify those at high risk for developing PD...
  82. ncbi request reprint Use of bomb pulse carbon-14 to age senile plaques and neurofibrillary tangles in Alzheimer's disease
    Mark A Lovell
    From the Sanders Brown Center on Aging and Alzheimer s Disease Research Center, 101 Sanders Brown Bldg, University of Kentucky, Lexington 40536 0230, USA
    Neurobiol Aging 23:179-86. 2002
    ..In addition, the data show that these structures, once formed, have a much slower carbon turnover rate than normal brain and are not in a formation/enzymatic degradation equilibrium...
  83. pmc Oxidatively modified RNA in mild cognitive impairment
    Mark A Lovell
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Neurobiol Dis 29:169-75. 2008
    ..In addition, levels of both adducts in MCI were comparable to those measured in LAD, suggesting RNA oxidation may be an early event in the pathogenesis of neuron degeneration in AD...
  84. ncbi request reprint Associations of cortical astrogliosis with cognitive performance and dementia status
    Michael L Kashon
    Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV 26505, USA
    J Alzheimers Dis 6:595-604; discussion 673-81. 2004
    ..Our findings underscore the need to look beyond standard neuropathological measures putatively linked to specific neuropathological conditions in efforts to identify common cellular and molecular processes that contribute to dementia...
  85. pmc 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
    D Allan Butterfield
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Brain Res 1148:243-8. 2007
    ..Immunohistochemistry analysis of hippocampus confirmed this result. These findings suggest that nitrosative damage occurs early in the course of MCI, and that protein nitration may be important for conversion of MCI to AD...

Research Grants14

  1. OXIDATIVE STRESS IN ALZHEIMER'S DISEASE
    William Markesbery; Fiscal Year: 2006
    ..This program project has the potential of identifying molecular targets for development of therapeutic agents aimed at decreasing neuron injury and improving the outcome of AD. ..
  2. PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUM
    William Markesbery; Fiscal Year: 2007
    ..This is the largest national and international prevention trial of AD and is based on an innovative and inter-institute collaborative sub-study model that is uniquely cost effective ..
  3. PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUM
    William Markesbery; Fiscal Year: 2006
    ..In addition, it will evaluate the effect of antioxidant therapy in a group of 200 elderly longitudinally followed normal controls. ..
  4. ALZHEIMER'S DISEASE RESEARCH CENTER
    William Markesbery; Fiscal Year: 2005
    ..Geddes); "Novel Peptide Inhibitors of Abeta accumulation and action" (Project 3, Dr. Estus), and "Lipid peroxidation, antioxidants in AD" (Project 4, D. Montine). Pilot studies will be determined annually. ..
  5. Prevention of Alzheimer's Diseae by Vitamin E and Selenium
    William Markesbery; Fiscal Year: 2009
    ....