Research Topics
Genomes and Genes | William MarkesberySummaryAffiliation: University of Kentucky Country: USA Publications
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Publications
Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brainKarrie E Grear
Department of Physiology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, USA
Mol Neurodegener 4:46. 2009..abstract:..
Damage to lipids, proteins, DNA, and RNA in mild cognitive impairmentWilliam 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...- DNA oxidation in Alzheimer's diseaseWilliam R Markesbery
Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky 40536 0230, USA
Antioxid Redox Signal 8:2039-45. 2006.... - Lewy body pathology in normal elderly subjectsWilliam 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... - Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairmentWilliam 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... - Neuropathologic substrate of mild cognitive impairmentWilliam 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)... - Neuropathologic alterations in mild cognitive impairment: a reviewWilliam 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... - 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... - 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 diseaseMuthuswamy 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... - Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1Alessandra 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... - Identification of nitrated proteins in Alzheimer's disease brain using a redox proteomics approachRukhsana 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... - 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 diseaseMiranda 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... - Oxidative modification and down-regulation of Pin1 in Alzheimer's disease hippocampus: A redox proteomics analysisRukhsana 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... - Early life linguistic ability, late life cognitive function, and neuropathology: findings from the Nun StudyKathryn 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... - Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer diseaseJoseph 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... - Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in miceChrista 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... - Oxidative damage in brain from human mutant APP/PS-1 double knock-in mice as a function of ageHafiz 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... 
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 diseaseTanea 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...- Proteomic identification of nitrated proteins in Alzheimer's disease brainAlessandra Castegna
Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, Kentucky 40506 0055, USA
J Neurochem 85:1394-401. 2003.... - Redox proteomics identification of oxidized proteins in Alzheimer's disease hippocampus and cerebellum: an approach to understand pathological and biochemical alterations in ADRukhsana 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... - Seleno-L-methionine protects against beta-amyloid and iron/hydrogen peroxide-mediated neuron deathShuling Xiong
Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536, USA
Antioxid Redox Signal 9:457-67. 2007.... - Alterations of zinc transporter proteins ZnT-1, ZnT-4 and ZnT-6 in preclinical Alzheimer's disease brainGanna 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... - Oxidative stress in head trauma in agingChangxing 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... - Preclinical Alzheimer disease: brain oxidative stress, Abeta peptide and proteomicsChristopher 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... - Proteomic identification of HNE-bound proteins in early Alzheimer disease: Insights into the role of lipid peroxidation in the progression of ADTanea 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.... - Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun StudyKathryn 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... - Ribosome dysfunction is an early event in Alzheimer's diseaseQunxing Ding
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky 40536-0230, USA
J Neurosci 25:9171-5. 2005.... - Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairmentJianquan 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... - Proteasome inhibition increases DNA and RNA oxidation in astrocyte and neuron culturesQunxing Ding
Department of Anatomy and Neurobiology, University of Kentucky, Lexington, Kentucky, USA
J Neurochem 91:1211-8. 2004.... - Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71Alessandra 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... - Omega-3 fatty acids: potential role in the management of early Alzheimer's diseaseGregory 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... - Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles "do count" when staging disease severityPeter 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... - Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationshipPeter 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... - Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer's diseaseMark A Lovell
Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
Nucleic Acids Res 35:7497-504. 2007.... - Abeta solubility and deposition during AD progression and in APPxPS-1 knock-in miceM 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... - Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer's disease brainChangxing 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... - Quantitative changes in the mitochondrial proteome from subjects with mild cognitive impairment, early stage, and late stage Alzheimer's diseaseBert 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... - Association between male gender and cortical Lewy body pathology in large autopsy seriesPeter 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... - Low sensitivity in clinical diagnoses of dementia with Lewy bodiesPeter 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... - Comparison of recruitment efforts targeted at primary care physicians versus the community at large for participation in Alzheimer disease clinical trialsSarah 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... - Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer diseasePeter 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... - Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 miceMark 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... - Acetylcholinesterase inhibitor treatment is associated with relatively slow cognitive decline in patients with Alzheimer's disease and AD + DLBPeter 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... - Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairmentPeter 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... - Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly personsPeter 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... - Proteomic identification of nitrated brain proteins in early Alzheimer's disease inferior parietal lobuleTanea 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... - Quantitative proteomic analysis of mitochondria from primary neuron cultures treated with amyloid beta peptideMark 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... - Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's diseaseD 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... - 3alpha,5alpha-THP: a potential plasma neurosteroid biomarker in Alzheimer's disease and perhaps non-Alzheimer's dementiaCharles 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)... - Ectopic expression of Musashi-1 in Alzheimer disease and Pick diseaseMark 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... - Biophysical and biochemical characterization of the intrinsic fluorescence from neurofibrillary tanglesGuoying 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... - Induction of hyperphosphorylated tau in primary rat cortical neuron cultures mediated by oxidative stress and glycogen synthase kinase-3Mark 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... - Designing a large prevention trial: statistical issuesRichard 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... - Wilms' tumor suppressor (WT1) is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer's diseaseMark 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... - Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acidMark 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.... - Human cerebral neuropathology of Type 2 diabetes mellitusPeter 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... - Association of HFE mutations with neurodegeneration and oxidative stress in Alzheimer's disease and correlation with APOEJoseph F Pulliam
Department of Pathology, University of Kentucky, Lexington, Kentucky 40536, USA
Am J Med Genet B Neuropsychiatr Genet 119:48-53. 2003.... - 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 developmentAvindra 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... - Alzheimer's disease and head circumferencePatricio 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... - Elevated zinc transporter-6 in mild cognitive impairment, Alzheimer disease, and pick diseaseMark 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... - Age and gender effects on human brain anatomy: a voxel-based morphometric study in healthy elderlyCharles 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... - Amyloid beta peptide, 4-hydroxynonenal and apoptosisMark 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... - Small head circumference is associated with less education in persons at risk for Alzheimer disease in later lifeJames 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... - Head circumference, education and risk of dementia: findings from the Nun StudyJames 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... - Healthy ageing in the Nun Study: definition and neuropathologic correlatesSuzanne 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... - Kalirin is under-expressed in Alzheimer's disease hippocampusHyeSook 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... - Defective DNA base excision repair in brain from individuals with Alzheimer's disease and amnestic mild cognitive impairmentLior 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... - TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutationsManuela 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... - Oxidative damage in mild cognitive impairment and early Alzheimer's diseaseMark 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... - Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participantsLon 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... - Cerebrospinal fluid lipoprotein delivery to human neuronal cells is increased in Alzheimer's disease and is dependent on apoE monomer concentrationCasey N Bassett
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
J Alzheimers Dis 4:19-30. 2002.... - The nitration product 5-nitro-gamma-tocopherol is increased in the Alzheimer brainKelly 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... - 4-Hydroxynonenal oxidatively modifies histones: implications for Alzheimer's diseaseJennifer 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... - F2-isoprostanes in Alzheimer and other neurodegenerative diseasesThomas 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... - Toll-like receptor-4 mediates neuronal apoptosis induced by amyloid beta-peptide and the membrane lipid peroxidation product 4-hydroxynonenalSung 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... - Decreased RNA, and increased RNA oxidation, in ribosomes from early Alzheimer's diseaseQunxing 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... - Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse modelsJoshua 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... - Under-expression of Kalirin-7 Increases iNOS activity in cultured cells and correlates to elevated iNOS activity in Alzheimer's disease hippocampusHyeSook 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... - Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's diseaseTaufika 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... - Isolation of neural precursor cells from Alzheimer's disease and aged control postmortem brainMark 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... - Association of olfactory dysfunction with incidental Lewy bodiesG 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... - Use of bomb pulse carbon-14 to age senile plaques and neurofibrillary tangles in Alzheimer's diseaseMark 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... - Oxidatively modified RNA in mild cognitive impairmentMark 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... - Associations of cortical astrogliosis with cognitive performance and dementia statusMichael 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... - 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 diseaseD 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 Grants
- OXIDATIVE STRESS IN ALZHEIMER'S DISEASEWilliam 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. ..
- PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUMWilliam 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 ..
- PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUMWilliam Markesbery; Fiscal Year: 2006..In addition, it will evaluate the effect of antioxidant therapy in a group of 200 elderly longitudinally followed normal controls. ..
- ALZHEIMER'S DISEASE RESEARCH CENTERWilliam 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. ..
- Prevention of Alzheimer's Diseae by Vitamin E and SeleniumWilliam Markesbery; Fiscal Year: 2009....