CoChat
Sign Up
Cited by 337Alzheimer's disease research and treatmentsEpigenetics and DNA MethylationDementia and Cognitive Impairment Research

Epigenetics, oxidative stress, and Alzheimer disease

Open access
Zawia, Nasser H., Lahiri, Debomoy K., Cardozo-Pelaez, Fernando·2009·Free Radical Biology and Medicine
DOI 10.1016/j.freeradbiomed.2009.02.006PMC PMC2673453
Open this paper in CoChat — free account

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disorder whose clinical manifestations appear in old age. The sporadic nature of 90% of AD cases, the differential susceptibility to and course of the illness, as well as the late age onset of the disease suggest that epigenetic and environmental components play a role in the etiology of late-onset AD. Animal exposure studies demonstrated that AD may begin early in life and may involve an interplay between the environment, epigenetics, and oxidative stress. Early life exposure of rodents and primates to the xenobiotic metal lead (Pb) enhanced the expression of genes associated with AD, repressed the expression of others, and increased the burden of oxidative DNA damage in the aged brain. Epigenetic mechanisms that control gene expression and promote the accumulation of oxidative DNA damage are mediated through alterations in the methylation or oxidation of CpG dinucleotides. We found that environmental influences occurring during brain development inhibit DNA-methyltransferases, thus hypomethylating promoters of genes associated with AD such as the beta-amyloid precursor protein (APP). This early life imprint was sustained and triggered later in life to increase the levels of APP and amyloid-beta (Abeta). Increased Abeta levels promoted the production of reactive oxygen species, which damage DNA and accelerate neurodegenerative events. Whereas AD-associated genes were overexpressed late in life, others were repressed, suggesting that these early life perturbations result in hypomethylation as well as hypermethylation of genes. The hypermethylated genes are rendered susceptible to Abeta-enhanced oxidative DNA damage because methylcytosines restrict repair of adjacent hydroxyguanosines. Although the conditions leading to early life hypo- or hypermethylation of specific genes are not known, these changes can have an impact on gene expression and imprint susceptibility to oxidative DNA damage in the aged brain.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.freeradbiomed.2009.02.006

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 104

  1. [1]Holliday R Epigenetics: a historical overview Epigenetics 1 76 80 2006 17998809
  2. [2]Morange M The relations between genetics and epigenetics: a historical point of view Ann N Y Acad Sci 981 50 60 2002 12547673
  3. [3]Bird A DNA methylation patterns and epigenetic memory Genes Dev 16 6 21 2002 11782440
  4. [4]Mulero-Navarro S Esteller M Epigenetic biomarkers for human cancer: the time is now Crit Rev Oncol Hematol 68 1 11 2008 18430583
  5. [5]Sutcliffe JS Nelson DL Zhang F Pieretti M Caskey CT Saxe D Warren ST DNA methylation represses FMR-1 transcription in fragile X syndrome Hum Mol Genet 1 397 400 1992 1301913
  6. [6]Malmgren H Steen-Bondeson ML Gustavson KH Seemanova E Holmgren G Oberle I Mandel JL Pettersson U Dahl N Methylation and mutation patterns in the fragile X syndrome Am J Med Genet 43 268 78 1992 1605200
  7. [7]Akbarian S The neurobiology of Rett syndrome Neuroscientist 9 57 63 2003 12580340
  8. [8]de Vries BB Jansen CC Duits AA Verheij C Willemsen R van Hemel JO van den Ouweland AM Niermeijer MF Oostra BA Halley DJ Variable FMR1 gene methylation of large expansions leads to variable phenotype in three males from one fragile X family J Med Genet 33 1007 10 1996 9004132 PMC1050811
  9. [9]Akbarian S Jiang Y Laforet G The molecular pathology of Rett syndrome: synopsis and update Neuromolecular Med 8 485 94 2006 17028371
  10. [11]Abdolmaleky HM Cheng KH Faraone SV Wilcox M Glatt SJ Gao F Smith CL Shafa R Aeali B Carnevale J Pan H Papageorgis P Ponte JF Sivaraman V Tsuang MT Thiagalingam S Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder Hum Mol Genet 15 3132 45 2006 16984965 PMC2799943
  11. [12]Abdolmaleky HM Cheng KH Russo A Smith CL Faraone SV Wilcox M Shafa R Glatt SJ Nguyen G Ponte JF Thiagalingam S Tsuang MT Hypermethylation of the reelin (RELN) promoter in the brain of schizophrenic patients: a preliminary report Am J Med Genet B Neuropsychiatr Genet 134B 60 6 2005 15717292
  12. [13]Abel T Zukin RS Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders Curr Opin Pharmacol 8 57 64 2008 18206423 PMC2405764
  13. [15]Pfister JA Ma C Morrison BE D’Mello SR Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity PLoS ONE 3 e4090 2008 19116652 PMC2605257
  14. [17]Robakis NK Ramakrishna N Wolfe G Wisniewski HM Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides Proc Natl Acad Sci U S A 84 4190 4 1987 3035574 PMC305050
  15. [18]Masters CL Simms G Weinman NA Multhaup G McDonald BL Beyreuther K Amyloid plaque core protein in Alzheimer disease and Down syndrome Proc Natl Acad Sci U S A 82 4245 9 1985 3159021 PMC397973
  16. [19]Selkoe DJ Abraham CR Podlisny MB Duffy LK Isolation of low-molecular-weight proteins from amyloid plaque fibers in Alzheimer’s disease J Neurochem 46 1820 34 1986 3517233
  17. [20]Goldgaber D Lerman MI McBride OW Saffiotti U Gajdusek DC Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease Science 235 877 80 1987 3810169
  18. [21]Glenner GG Wong CW Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein Biochem Biophys Res Commun 120 885 90 1984 6375662
  19. [22]McGurn B Deary IJ Starr JM Childhood cognitive ability and risk of late-onset Alzheimer and vascular dementia Neurology 71 1051 6 2008 18579804
  20. [23]Scarpa S Cavallaro RA D’Anselmi F Fuso A Gene silencing through methylation: an epigenetic intervention on Alzheimer disease J Alzheimers Dis 9 407 14 2006 16917149
  21. [24]Cacabelos R Pharmacogenomics in Alzheimer’s disease Methods Mol Biol 448 213 357 2008 18370236
  22. [25]Ancolio K Dumanchin C Barelli H Warter JM Brice A Campion D Frebourg T Checler F Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP) maturation by a new Val-715 --> Met betaAPP-770 mutation responsible for probable early-onset Alzheimer’s disease Proc Natl Acad Sci U S A 96 4119 24 1999 10097173 PMC22430
  23. [26]Eckman CB Mehta ND Crook R Perez-tur J Prihar G Pfeiffer E Graff-Radford N Hinder P Yager D Zenk B Refolo LM Prada CM Younkin SG Hutton M Hardy J A new pathogenic mutation in the APP gene (I716V) increases the relative proportion of A beta 42(43) Hum Mol Genet 6 2087 9 1997 9328472
  24. [27]Haass C Hung AY Selkoe DJ Teplow DB Mutations associated with a locus for familial Alzheimer’s disease result in alternative processing of amyloid beta-protein precursor J Biol Chem 269 17741 8 1994 8021287
  25. [28]Suzuki N Cheung TT Cai XD Odaka A Otvos L Jr Eckman C Golde TE Younkin SG An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants Science 264 1336 40 1994 8191290
  26. [29]Bertram L Tanzi RE Alzheimer’s disease: one disorder, too many genes? Hum Mol Genet 13 Spec No 1 R135 41 2004 14764623
  27. [30]Gatz M Pedersen NL Berg S Johansson B Johansson K Mortimer JA Posner SF Viitanen M Winblad B Ahlbom A Heritability for Alzheimer’s disease: the study of dementia in Swedish twins J Gerontol A Biol Sci Med Sci 52 M117 25 1997 9060980
  28. [31]Gatz M Fratiglioni L Johansson B Berg S Mortimer JA Reynolds CA Fiske A Pedersen NL Complete ascertainment of dementia in the Swedish Twin Registry: the HARMONY study Neurobiol Aging 26 439 47 2005 15653172
  29. [32]Raiha I Kaprio J Koskenvuo M Rajala T Sourander L Alzheimer’s disease in twins Biomed Pharmacother 51 101 4 1997 9181044
  30. [33]Wang SC Oelze B Schumacher A Age-specific epigenetic drift in late-onset Alzheimer’s disease PLoS ONE 3 e2698 2008 18628954 PMC2444024
  31. [34]Moreira PI Nunomura A Nakamura M Takeda A Shenk JC Aliev G Smith MA Perry G Nucleic acid oxidation in Alzheimer disease Free Radic Biol Med 44 1493 505 2008 18258207
  32. [35]Marcus DL Thomas C Rodriguez C Simberkoff K Tsai JS Strafaci JA Freedman ML Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer’s disease Exp Neurol 150 40 4 1998 9514828
  33. [36]Dizdaroglu M Jaruga P Birincioglu M Rodriguez H Free radical-induced damage to DNA: mechanisms and measurement Free Radic Biol Med 32 1102 15 2002 12031895
  34. [37]Einolf HJ Schnetz-Boutaud N Guengerich FP Steady-state and pre-steady-state kinetic analysis of 8-oxo-7,8-dihydroguanosine triphosphate incorporation and extension by replicative and repair DNA polymerases Biochemistry 37 13300 12 1998 9748338
  35. [38]Hayakawa H Taketomi A Sakumi K Kuwano M Sekiguchi M Generation and elimination of 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate, a mutagenic substrate for DNA synthesis, in human cells Biochemistry 34 89 95 1995 7819228
  36. [39]Ghosh R Mitchell DL Effect of oxidative DNA damage in promoter elements on transcription factor binding Nucleic Acids Res 27 3213 8 1999 10454620 PMC148550
  37. [40]Valinluck V Tsai HH Rogstad DK Burdzy A Bird A Sowers LC Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2) Nucleic Acids Res 32 4100 8 2004 15302911 PMC514367
  38. [41]Barker DJ Winter PD Osmond C Margetts B Simmonds SJ Weight in infancy and death from ischaemic heart disease Lancet 2 577 80 1989 2570282
  39. [42]Barker DJ Fetal origins of cardiovascular disease Ann Med 31 Suppl 1 3 6 1999 10342493
  40. [43]Barker DJ Eriksson JG Forsen T Osmond C Fetal origins of adult disease: strength of effects and biological basis Int J Epidemiol 31 1235 9 2002 12540728
  41. [45]Yarbrough DE Barrett-Connor E Kritz-Silverstein D Wingard DL Birth weight, adult weight, and girth as predictors of the metabolic syndrome in postmenopausal women: the Rancho Bernardo Study Diabetes Care 21 1652 8 1998 9773725
  42. [46]Valdez R Athens MA Thompson GH Bradshaw BS Stern MP Birthweight and adult health outcomes in a biethnic population in the USA Diabetologia 37 624 31 1994 7926349
  43. [47]Weaver IC Cervoni N Champagne FA D’Alessio AC Sharma S Seckl JR Dymov S Szyf M Meaney MJ Epigenetic programming by maternal behavior Nat Neurosci 7 847 54 2004 15220929
  44. [48]Bilbo SD Levkoff LH Mahoney JH Watkins LR Rudy JW Maier SF Neonatal infection induces memory impairments following an immune challenge in adulthood Behav Neurosci 119 293 301 2005 15727533
  45. [49]Boksa P El-Khodor BF Birth insult interacts with stress at adulthood to alter dopaminergic function in animal models: possible implications for schizophrenia and other disorders Neurosci Biobehav Rev 27 91 101 2003 12732226
  46. [50]Dalman C Cullberg J Neonatal hyperbilirubinaemia--a vulnerability factor for mental disorder? Acta Psychiatr Scand 100 469 71 1999 10626927
  47. [51]Preti A Fetal hypoxia, genetic risk, and schizophrenia Am J Psychiatry 160 1186 author reply 1186 2003 12777283
  48. [52]Gluckman PD Hanson MA Living with the past: evolution, development, and patterns of disease Science 305 1733 6 2004 15375258
  49. [53]Toscano CD Guilarte TR Lead neurotoxicity: from exposure to molecular effects Brain Res Brain Res Rev 49 529 54 2005 16269318
  50. [54]Needleman HL Leviton A Lead and neurobehavioural deficit in children Lancet 2 104 1979 87956
  51. [55]Winneke G Kramer U Brockhaus A Ewers U Kujanek G Lechner H Janke W Neuropsychological studies in children with elevated tooth-lead concentrations. II. Extended study Int Arch Occup Environ Health 51 231 52 1983 6852930
  52. [56]Gorell JM Rybicki BA Cole Johnson C Peterson EL Occupational metal exposures and the risk of Parkinson’s disease Neuroepidemiology 18 303 8 1999 10545782
  53. [57]Kamel F Umbach DM Munsat TL Shefner JM Hu H Sandler DP Lead exposure and amyotrophic lateral sclerosis Epidemiology 13 311 9 2002 11964933
  54. [58]Stewart WF Schwartz BS Simon D Kelsey K Todd AC ApoE genotype, past adult lead exposure, and neurobehavioral function Environ Health Perspect 110 501 5 2002 12003753 PMC1240838
  55. [59]Stewart WF Schwartz BS Davatzikos C Shen D Liu D Wu X Todd AC Shi W Bassett S Youssem D Past adult lead exposure is linked to neurodegeneration measured by brain MRI Neurology 66 1476 84 2006 16717205
  56. [60]Basha MR Wei W Bakheet SA Benitez N Siddiqi HK Ge YW Lahiri DK Zawia NH The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain J Neurosci 25 823 9 2005 15673661 PMC6725614
  57. [61]Wu J Basha MR Brock B Cox DP Cardozo-Pelaez F McPherson CA Harry J Rice DC Maloney B Chen D Lahiri DK Zawia NH Alzheimer’s disease (AD)-like pathology in aged monkeys after infantile exposure to environmental metal lead (Pb): evidence for a developmental origin and environmental link for AD J Neurosci 28 3 9 2008 18171917 PMC2486412
  58. [62]Smith MA Perry G Free radical damage, iron, and Alzheimer’s disease J Neurol Sci 134 Suppl 92 4 1995 8847550
  59. [64]Cecchi C Fiorillo C Sorbi S Latorraca S Nacmias B Bagnoli S Nassi P Liguri G Oxidative stress and reduced antioxidant defenses in peripheral cells from familial Alzheimer’s patients Free Radic Biol Med 33 1372 9 2002 12419469
  60. [65]Lovell MA Gabbita SP Markesbery WR Increased DNA oxidation and decreased levels of repair products in Alzheimer’s disease ventricular CSF J Neurochem 72 771 6 1999 9930752
  61. [66]Bolin CM Basha R Cox D Zawia NH Maloney B Lahiri DK Cardozo-Pelaez F Exposure to lead and the developmental origin of oxidative DNA damage in the aging brain Faseb J 20 788 90 2006 16484331
  62. [67]Evans MD Cooke MS Factors contributing to the outcome of oxidative damage to nucleic acids Bioessays 26 533 42 2004 15112233
  63. [68]Bestor TH The DNA methyltransferases of mammals Hum Mol Genet 9 2395 402 2000 11005794
  64. [69]Wu G Bazer FW Cudd TA Meininger CJ Spencer TE Maternal nutrition and fetal development J Nutr 134 2169 72 2004 15333699
  65. [70]Santos F Hendrich B Reik W Dean W Dynamic reprogramming of DNA methylation in the early mouse embryo Dev Biol 241 172 82 2002 11784103
  66. [71]Weaver IC Diorio J Seckl JR Szyf M Meaney MJ Early environmental regulation of hippocampal glucocorticoid receptor gene expression: characterization of intracellular mediators and potential genomic target sites Ann N Y Acad Sci 1024 182 212 2004 15265782
  67. [72]Lillycrop KA Phillips ES Jackson AA Hanson MA Burdge GC Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring J Nutr 135 1382 6 2005 15930441
  68. [73]Poirier LA Vlasova TI The prospective role of abnormal methyl metabolism in cadmium toxicity Environ Health Perspect 110 Suppl 5 793 5 2002 12426133 PMC1241247
  69. [74]Takiguchi M Achanzar WE Qu W Li G Waalkes MP Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation Exp Cell Res 286 355 65 2003 12749863
  70. [75]Ballestar E Esteller M The epigenetic breakdown of cancer cells: from DNA methylation to histone modifications Prog Mol Subcell Biol 38 169 81 2005 15881895
  71. [76]Foster WG McMahon A Rice DC Sperm chromatin structure is altered in cynomolgus monkeys with environmentally relevant blood lead levels Toxicol Ind Health 12 723 35 1996 8989849
  72. [77]Quintanilla-Vega B HD Bal W Silbergeld EK Waalkes MP Anderson LD Lead effects on protamine-DNA binding Am J Ind Med 38 324 329 2000 10940971
  73. [78]Salbaum JM Weidemann A Masters CL Beyreuther K The promoter of Alzheimer’s disease amyloid A4 precursor gene Prog Clin Biol Res 317 277 83 1989 2690103
  74. [79]Pollwein P Masters CL Beyreuther K The expression of the amyloid precursor protein (APP) is regulated by two GC-elements in the promoter Nucleic Acids Res 20 63 8 1992 1738605 PMC310326
  75. [80]Lukiw WJ Rogaev EI Wong L Vaula G McLachlan DR St George Hyslop P Protein-DNA interactions in the promoter region of the amyloid precursor protein (APP) gene in human neocortex Brain Res Mol Brain Res 22 121 31 1994 8015372
  76. [81]Hoffman PW Chernak JM DNA binding and regulatory effects of transcription factors SP1 and USF at the rat amyloid precursor protein gene promoter Nucleic Acids Res 23 2229 35 1995 7610052 PMC307012
  77. [82]Querfurth HW Jiang J Xia W Selkoe DJ Enhancer function and novel DNA binding protein activity in the near upstream betaAPP gene promoter Gene 232 125 41 1999 10333529
  78. [83]Milici A Salbaum JM Beyereuther K Study of the Alzheimer’s A4 precursor gene promoter region by genomic sequencing using Taq polymerase Biochem Biophys Res Commun 169 46 50 1990 1972017
  79. [84]Rogaev EI Lukiw WJ Lavrushina O Rogaeva EA St George-Hyslop PH The upstream promoter of the beta-amyloid precursor protein gene (APP) shows differential patterns of methylation in human brain Genomics 22 340 7 1994 7528717
  80. [85]Tohgi H Utsugisawa K Nagane Y Yoshimura M Genda Y Ukitsu M Reduction with age in methylcytosine in the promoter region −224 approximately −101 of the amyloid precursor protein gene in autopsy human cortex Brain Res Mol Brain Res 70 288 92 1999 10407177
  81. [86]Nagane Y Utsugisawa K Tohgi H PCR amplification in bisulfite methylcytosine mapping in the GC-rich promoter region of amyloid precursor protein gene in autopsy human brain Brain Res Brain Res Protoc 5 167 71 2000 10775837
  82. [87]Fuso A Seminara L Cavallaro RA D’Anselmi F Scarpa S S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production Mol Cell Neurosci 28 195 204 2005 15607954
  83. [88]Mancini DN Singh SM Archer TK Rodenhiser DI Site-specific DNA methylation in the neurofibromatosis (NF1) promoter interferes with binding of CREB and SP1 transcription factors Oncogene 18 4108 19 1999 10435592
  84. [89]Clark SJ Harrison J Molloy PL Sp1 binding is inhibited by (m)Cp(m)CpG methylation Gene 195 67 71 1997 9300822
  85. [90]Wong WK Chen K Shih JC Decreased methylation and transcription repressor Sp3 up-regulated human monoamine oxidase (MAO) B expression during Caco-2 differentiation J Biol Chem 278 36227 35 2003 12855685
  86. [91]Zhu WG Srinivasan K Dai Z Duan W Druhan LJ Ding H Yee L Villalona-Calero MA Plass C Otterson GA Methylation of adjacent CpG sites affects Sp1/Sp3 binding and activity in the p21(Cip1) promoter Mol Cell Biol 23 4056 65 2003 12773551 PMC156121
  87. [92]Cao YX Jean JC Williams MC Cytosine methylation of an Sp1 site contributes to organ-specific and cell-specific regulation of expression of the lung epithelial gene t1alpha Biochem J 350 Pt 3 883 90 2000 10970805 PMC1221323
  88. [93]Ames BN Shigenaga MK Oxidants are a major contributor to aging Ann N Y Acad Sci 663 85 96 1992 1482105
  89. [94]Radicella JP Dherin C Desmaze C Fox MS Boiteux S Cloning and characterization of hOGG1, a human homolog of the OGG1 gene of Saccharomyces cerevisiae Proc Natl Acad Sci U S A 94 8010 5 1997 9223305 PMC21547
  90. [95]Mao G Pan X Zhu BB Zhang Y Yuan F Huang J Lovell MA Lee MP Markesbery WR Li GM Gu L Identification and characterization of OGG1 mutations in patients with Alzheimer’s disease Nucleic Acids Res 35 2759 66 2007 17426120 PMC1885677
  91. [96]Lovell MA Markesbery WR Oxidative DNA damage in mild cognitive impairment and late-stage Alzheimer’s disease Nucleic Acids Res 35 7497 504 2007 17947327 PMC2190704
  92. [97]Castellani RJ Lee HG Perry G Smith MA Antioxidant protection and neurodegenerative disease: the role of amyloid-beta and tau Am J Alzheimers Dis Other Demen 21 126 30 2006 16634469 PMC10833251
  93. [98]Ono K Hamaguchi T Naiki H Yamada M Anti-amyloidogenic effects of antioxidants: implications for the prevention and therapeutics of Alzheimer’s disease Biochim Biophys Acta 1762 575 86 2006 16644188
  94. [100]Obregon DF Rezai-Zadeh K Bai Y Sun N Hou H Ehrhart J Zeng J Mori T Arendash GW Shytle D Town T Tan J ADAM10 activation is required for green tea (−)-epigallocatechin-3-gallate-induced alpha-secretase cleavage of amyloid precursor protein J Biol Chem 281 16419 27 2006 16624814
  95. [102]Yatin SM Varadarajan S Butterfield DA Vitamin E Prevents Alzheimer’s Amyloid beta-Peptide (1–42)-Induced Neuronal Protein Oxidation and Reactive Oxygen Species Production J Alzheimers Dis 2 123 131 2000 12214102
  96. [103]Weitzman SA Turk PW Milkowski DH Kozlowski K Free radical adducts induce alterations in DNA cytosine methylation Proc Natl Acad Sci U S A 91 1261 4 1994 8108398 PMC43137
  97. [104]Turk PW Laayoun A Smith SS Weitzman SA DNA adduct 8-hydroxyl-2′-deoxyguanosine (8-hydroxyguanine) affects function of human DNA methyltransferase Carcinogenesis 16 1253 5 1995 7767994
  98. [105]Chan A Shea TB Supplementation with apple juice attenuates presenilin-1 overexpression during dietary and genetically-induced oxidative stress J Alzheimers Dis 10 353 358 2006 17183144
  99. [106]Lahiri DK Where the actions of environment (nutrition) gene and protein meet: Beneficial role of fruit and vegetables juices in potentially delaying the onset of Alzheimer’s disease J Alzheimers Dis 10 359 361 2006 17183145
  100. [107]Gehring M Reik W Henikoff S DNA demethylation by DNA repair Trends Genet 2009 19144439
  101. [108]Bhattacharya SK Ramchandani S Cervoni N Szyf M A mammalian protein with specific demethylase activity for mCpG DNA Nature 397 579 83 1999 10050851
  102. [109]Bjornsson HT Sigurdsson MI Fallin MD Irizarry RA Aspelund T Cui H Yu W Rongione MA Ekstrom TJ Harris TB Launer LJ Eiriksdottir G Leppert MF Sapienza C Gudnason V Feinberg AP Intra-individual change over time in DNA methylation with familial clustering JAMA 299 2877 83 2008 18577732 PMC2581898
  103. [110]Lahiri DK Maloney B Basha MR Ge YW Zawia NH How and when environmental agents and dietary factors affect the course of Alzheimer’s disease: the “LEARn” model (Latent Early Associated Regulation) may explain the triggering of AD Current Alzheimer Research 4 219 228 2007 17430250
  104. [111]Lu T Pan Y Kao SY Li C Kohane I Chan J Yankner BA Gene regulation and DNA damage in the ageing human brain Nature 429 883 91 2004 15190254

Cited by

Sorted by citations

Authors
Zawia, N. H., Lahiri, D. K., & Cardozo-Pelaez, F.
Affiliations
  • University of Rhode Island (US)
  • Indiana University School of Medicine (US)
Corresponding author
Zawia, Nasser H.
ORCID
Lahiri, Debomoy K.
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2009-05
Volume
46
Issue
9
Pages
1241-1249
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/j.freeradbiomed.2009.02.006
PMC
PMC2673453
OpenAlex
W2159677246
Cited by
337
References
7
Citations by year
2026: 3 · 2025: 5 · 2024: 17 · 2023: 8 · 2022: 8 · 2021: 14 · 2020: 20 · 2019: 19 · 2018: 12 · 2017: 15 · 2016: 28 · 2015: 21 · 2014: 27 · 2013: 33 · 2012: 33
FWCI
3.91
Type
journal article
Language
en
Open access
Licence
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Journal of Media Literacy Education (submittedVersion, cc-by-nc-nd)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • National Institute on Aging (AG 18379, R01AG018884, R15AG023604, R03AG027246, AG 023604, AG18884, AG 027246, R01AG018379)
  • National Institute of Environmental Health Sciences (ES013022, R01ES015867, R56ES015867, R21ES013022)
  • National Center for Research Resources (P20RR016457, P20RR015583, P20RR017670)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, epigenetics, oxidative stress, oxidative DNA damage, DNA methylation, lead exposure, early life exposure, DNA methyltransferases, amyloid precursor protein, amyloid-beta, reactive oxygen species, CpG methylation, gene expression regulation, neurodegeneration, brain aging
MeSH terms
Age Factors, Alzheimer Disease, Animals, DNA Damage, Environmental Exposure, Gene Expression Regulation, Humans, Lead, Oxidation-Reduction, Receptors, Cell Surface, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Oxidative Stress, DNA Methylation, Genetic Predisposition to Disease, Epigenesis, Genetic, Protease Nexins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review