William R Markesbery

Summary

Affiliation: University of Kentucky
Country: USA

Publications

  1. ncbi request reprint Oxidative alterations in Alzheimer's disease
    W R Markesbery
    Sanders Brown Center on Aging and Alzheimer s Disease Research Center, Department of Pathology, University of Kentucky Medical Center, Lexington, USA
    Brain Pathol 9:133-46. 1999
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. pmc Proteomic identification of specifically carbonylated brain proteins in APP(NLh)/APP(NLh) × PS-1(P264L)/PS-1(P264L) human double mutant knock-in mice model of Alzheimer disease as a function of age
    Rukhsana Sultana
    Department of Chemistry, Center of Membrane Sciences, and Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA
    J Proteomics 74:2430-40. 2011
  9. 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
  10. 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

Collaborators

Detail Information

Publications125 found, 100 shown here

  1. ncbi request reprint Oxidative alterations in Alzheimer's disease
    W R Markesbery
    Sanders Brown Center on Aging and Alzheimer s Disease Research Center, Department of Pathology, University of Kentucky Medical Center, Lexington, USA
    Brain Pathol 9:133-46. 1999
    ....
  2. 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...
  3. 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. pmc Proteomic identification of specifically carbonylated brain proteins in APP(NLh)/APP(NLh) × PS-1(P264L)/PS-1(P264L) human double mutant knock-in mice model of Alzheimer disease as a function of age
    Rukhsana Sultana
    Department of Chemistry, Center of Membrane Sciences, and Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA
    J Proteomics 74:2430-40. 2011
    ..We found a number of proteins that are oxidatively modified in APP/PS1 mice compared to age-matched controls. The relevance of the identified proteins to the progression and pathogenesis of AD is discussed...
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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...
  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 Proteomic analysis of brain proteins in APP/PS-1 human double mutant knock-in mice with increasing amyloid β-peptide deposition: insights into the effects of in vivo treatment with N-acetylcysteine as a potential therapeutic intervention in mild cognitive
    Renã A S Robinson
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    Proteomics 11:4243-56. 2011
    ..Overall, the proteomic results support the notion that NAC may be beneficial for increasing cellular stress responses in WT mice and for influencing the levels of energy- and mitochondria-related proteins in APP/PS-1 mice...
  18. 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...
  19. 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...
  20. 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...
  21. doi request reprint Redox proteomics analysis of brains from subjects with amnestic mild cognitive impairment compared to brains from subjects with preclinical Alzheimer's disease: insights into memory loss in MCI
    Christopher D Aluise
    Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA
    J Alzheimers Dis 23:257-69. 2011
    ..Our data suggest that marked changes occur at the protein level in MCI that may cause or reflect memory loss and other AD symptoms...
  22. 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
    ....
  23. 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...
  24. 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...
  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. 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...
  27. 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...
  28. 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...
  29. 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)...
  30. 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...
  31. 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...
  32. 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...
  33. 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...
  34. 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
    ....
  35. 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...
  36. 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...
  37. 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...
  38. 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
    ....
  39. 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...
  40. 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...
  41. ncbi request reprint Altered expression of zinc transporters-4 and -6 in mild cognitive impairment, early and late Alzheimer's disease brain
    J L Smith
    Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
    Neuroscience 140:879-88. 2006
    ..05) increased in hippocampus/parahippocampal gyrus of early Alzheimer's disease and Alzheimer's disease subjects. Zn transporter-6 is also increased (P<0.1) in the superior and middle temporal gyrus of Alzheimer's disease brain...
  42. 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...
  43. 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...
  44. 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...
  45. 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
    ....
  46. 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...
  47. pmc Elevated 4-hydroxyhexenal in Alzheimer's disease (AD) progression
    Melissa A Bradley
    Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
    Neurobiol Aging 33:1034-44. 2012
    ..Together these data support a role for lipid peroxidation in the progression of Alzheimer's disease...
  48. 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...
  49. 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...
  50. 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...
  51. 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...
  52. 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...
  53. 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...
  54. 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
    ....
  55. 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...
  56. 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...
  57. 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
    ....
  58. 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...
  59. 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...
  60. ncbi request reprint Potential in vivo amelioration by N-acetyl-L-cysteine of oxidative stress in brain in human double mutant APP/PS-1 knock-in mice: toward therapeutic modulation of mild cognitive impairment
    Quanzhen Huang
    Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, USA
    J Neurosci Res 88:2618-29. 2010
    ..These results are discussed with reference to the therapeutic potential of this brain-accessible glutathione precursor in the treatment of MCI and AD...
  61. ncbi request reprint The glial glutamate transporter, GLT-1, is oxidatively modified by 4-hydroxy-2-nonenal in the Alzheimer's disease brain: the role of Abeta1-42
    C M Lauderback
    Department of Chemistry, and Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky, USA
    J Neurochem 78:413-6. 2001
    ..Furthermore, our data suggests that Abeta may be a possible causative agent in this cascade...
  62. pmc The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life
    D Iacono
    Division of Neuropathology, Department of Pathology, Johns Hopkins University, School of Medicine, Ross Building 558, 720 Rutland Avenue, Baltimore, MD 21205, USA
    Neurology 73:665-73. 2009
    ..In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered...
  63. 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...
  64. ncbi request reprint Proteasome inhibition induces reversible impairments in protein synthesis
    Qunxing Ding
    205 Sanders Brown Center on Aging, 800 S Limestone, University of Kentucky, Lexington, Kentucky 40536 0230, USA
    FASEB J 20:1055-63. 2006
    ..Together these findings have important implications for understanding proteasome inhibition as a potential contributor to aging and age-related disease...
  65. 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...
  66. 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
    ....
  67. 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...
  68. 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...
  69. 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...
  70. 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...
  71. 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...
  72. ncbi request reprint Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease
    J Wang
    Department of Chemistry, University of Kentucky, Lexington, 40536, USA
    J Neurochem 93:953-62. 2005
    ..DNA from temporal lobe showed the most oxidative damage, whereas cerebellum was only slightly affected in AD brains. These results suggest that oxidative damage to mitochondrial DNA may contribute to the neurodegeneration of AD...
  73. ncbi request reprint Protein oxidation in the brain in Alzheimer's disease
    M Y Aksenov
    Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA
    Neuroscience 103:373-83. 2001
    ....
  74. ncbi request reprint Elevation of AKR7A2 (succinic semialdehyde reductase) in neurodegenerative disease
    M J Picklo
    Department of Pathology, Vanderbilt University Medical Center, C3321 A Medical Center North, Nashville, TN 37232, USA
    Brain Res 916:229-38. 2001
    ..Our data suggest that reactive gliosis, as a response to injury, may affect GHB neuromodulatory pathways in neurodegenerative disease and elevate aldehyde detoxification pathways...
  75. 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:..
  76. 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...
  77. 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...
  78. 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...
  79. 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...
  80. 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)...
  81. 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...
  82. 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...
  83. ncbi request reprint Decreased thioredoxin and increased thioredoxin reductase levels in Alzheimer's disease brain
    M A Lovell
    Sanders Brown Center on Aging, Departments of Chemistry, Neurology, and Pathology, University of Kentucky, Lexington, KY 40536 0230, USA
    Free Radic Biol Med 28:418-27. 2000
    ..This decrease in the antioxidant Trx-TR system may contribute to the increased oxidative stress and subsequent neurodegeneration observed in the brain in AD...
  84. ncbi request reprint Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer's disease
    M A Lovell
    Sanders Brown Center on Aging and Departments of Chemistry, Neurology and Pathology, University of Kentucky, Lexington, KY 40536, USA
    Neurotox Res 7:265-71. 2005
    ....
  85. ncbi request reprint "Preclinical" AD revisited: neuropathology of cognitively normal older adults
    F A Schmitt
    Sanders Brown Center on Aging and Alzheimer s Disease Research Center, Department of Neurology, University of Kentucky College of Medicine, Lexington 40536, USA
    Neurology 55:370-6. 2000
    ..To classify neuropathologic alterations in the brains of nondemented older adults using current sets of criteria for AD...
  86. ncbi request reprint Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures
    M A Lovell
    Sanders-Brown Center on Aging and Alzheimer's Disease Research Center, 101 Sanders-Brown Building, University of Kentucky, 800 South Limestone Street, Lexington, KY 40536-0230, USA
    Neurobiol Aging 22:187-94. 2001
    ..Collectively, these data show that acrolein is increased in the brain in AD and demonstrate neurotoxicity mechanisms that might be important in the pathogenesis of neuron degeneration in AD...
  87. ncbi request reprint Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study
    D A Snowdon
    Sanders Brown Center on Aging, and the Departments of Preventive Medicine, Neurology, and Pathology, College of Medicine, University of Kentucky, Lexington 40536 0230, USA
    Am J Clin Nutr 71:993-8. 2000
    ..Previous studies suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia, and Alzheimer disease-related neurodegeneration of the brain...
  88. ncbi request reprint Brain donation in normal aging: procedures, motivations, and donor characteristics from the Biologically Resilient Adults in Neurological Studies (BRAiNS) Project
    F A Schmitt
    Sanders Brown Center on Aging Alzheimer s Disease Research Center, Department of Neurology, University of Kentucky Medical Center, Lexington 40536, USA
    Gerontologist 41:716-22. 2001
    ..Within research settings, encouraging participant recruitment of friends or family members would likely increase tissue acquisition rates...
  89. ncbi request reprint White matter volumes and periventricular white matter hyperintensities in aging and dementia
    C D Smith
    Department of Neurology, University of Kentucky Medical Center, Lexington 40536, USA
    Neurology 54:838-42. 2000
    ..To determine the relationship between MRI periventricular white matter hyperintensities, cerebral white matter volumes, neuropathologic findings, and cognitive status in aged individuals...
  90. ncbi request reprint Expression of p53, bcl-2, E-cadherin, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 in paired primary tumors and brain metastasis
    S M Arnold
    Division of Hematology and Oncology, Markey Cancer Center, University of Kentucky, Lexington 40536, USA
    Clin Cancer Res 5:4028-33. 1999
    ..The high expression of EC may indicate the importance of adherence at late stages of metastasis but requires further study...
  91. ncbi request reprint Changes in thiol content and expression of glutathione redox system genes in the hippocampus and cerebellum in Alzheimer's disease
    M Y Aksenov
    Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Building, 800 South Limestone, Lexington, KY 40536-0230, USA
    Neurosci Lett 302:141-5. 2001
    ..This study suggests that protective antioxidant gene responses are insufficient to counteract the increased oxidative damage of proteins in a vulnerable region of the AD brain...
  92. ncbi request reprint Protection against amyloid beta peptide toxicity by zinc
    M A Lovell
    Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536 0230, USA
    Brain Res 823:88-95. 1999
    ..Together, these data suggest that Zn functions as a double-edged sword, affording protection against Abeta at low concentrations and enhancing toxicity at high concentrations...
  93. pmc Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies
    P T Nelson
    Department of Pathology, Division of Neuropathology, University of Kentucky Medical Center, 800 S Limestone, University of Kentucky, Lexington, KY 40536 0230, USA
    Neurology 73:1127-33. 2009
    ..Recent studies raised questions about the severity of cognitive impairment associated with dementia with Lewy bodies (DLB). However, there have been few analyses of large, multicenter data registries for clinical-pathologic correlation...
  94. ncbi request reprint Evidence of increased oxidative damage in subjects with mild cognitive impairment
    J N Keller
    Department of Anatomy, University of Kentucky, Lexington 40536 0230, USA
    Neurology 64:1152-6. 2005
    ..To determine if increased levels of oxidative damage are present in the brains of persons with mild cognitive impairment (MCI), a condition that often precedes Alzheimer disease (AD)...
  95. ncbi request reprint Critical decline in fine motor hand movements in human aging
    C D Smith
    Department of Neurology, Sanders Brown Center on Aging, University of Kentucky College of Medicine, Lexington, USA
    Neurology 53:1458-61. 1999
    ..Slowing of motor movements in human aging is a well-known occurrence, but its biologic basis is poorly understood. Reliable quantitation may refine observations of this phenomenon to better aid research on this entity...
  96. ncbi request reprint 4-hydroxynonenal increases neuronal susceptibility to oxidative stress
    J N Keller
    Sanders Brown Center on Aging, University of Kentucky, Lexington 40536 0230, USA
    J Neurosci Res 58:823-30. 1999
    ..In addition, the present study indicates a possible mechanism for reactive oxygen species and lipid peroxidation toxicity in neurodegenerative conditions...
  97. ncbi request reprint Brain structural alterations before mild cognitive impairment
    C D Smith
    MRISC, Room 62, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536
    Neurology 68:1268-73. 2007
    ..To determine whether alterations of brain structure in normal aged individuals precede the development of mild cognitive impairment (MCI) or Alzheimer disease (AD)...
  98. pmc Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease
    G A Jicha
    Department of Neurology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
    Neurobiol Aging 31:1805-13. 2010
    ....
  99. ncbi request reprint Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid
    M A Lovell
    University of Kentucky, Department of Chemistry, Sanders Brown Center on Aging, 101 Sanders Brown Bldg, 800 S Limestone St, Lexington, KY 40536 0230, USA
    Arch Neurol 58:392-6. 2001
    ....
  100. ncbi request reprint Vulnerability of synaptosomes from apoE knock-out mice to structural and oxidative modifications induced by A beta(1-40): implications for Alzheimer's disease
    C M Lauderback
    Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40506, USA
    Biochemistry 40:2548-54. 2001
    ..Together, these data support a role for apoE in the modulation of oxidative injury and in the maintenance of synaptic integrity and are discussed with reference to alterations in AD brain...
  101. ncbi request reprint Improved predictive model for pre-symptomatic mild cognitive impairment and Alzheimer's disease
    C D Smith
    Department of Neurology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
    Neurol Res 30:1091-6. 2008
    ..4 years after the scan. The objective of this study was to show whether accuracy of this predictive model was increased using an advanced segmentation technique...