Neurobiology of Aging
Volume 28, Issue 5 , Pages 648-676 , May 2007

Oxidative stress: A bridge between Down's syndrome and Alzheimer's disease

  • Marianna Zana

      Affiliations

    • Department of Psychiatry, Faculty of Medicine, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St, Szeged H-6725, Hungary
    • Alzheimer's Disease Research Center, Faculty of Medicine, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St, Szeged H-6725, Hungary
    • Corresponding Author InformationCorresponding author. Tel.: +36 62 545358; fax: +36 62 545973.
  • ,
  • Zoltán Janka

      Affiliations

    • Department of Psychiatry, Faculty of Medicine, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St, Szeged H-6725, Hungary
  • ,
  • János Kálmán

      Affiliations

    • Department of Psychiatry, Faculty of Medicine, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St, Szeged H-6725, Hungary
    • Alzheimer's Disease Research Center, Faculty of Medicine, Albert Szent-Györgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St, Szeged H-6725, Hungary

Received 30 November 2005 ,Revised 23 February 2006 ,Accepted 16 March 2006.

References 

  1. Abate C, Patel L, Rauscher FJ, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science. 1990;249(4973):1157–1161
  2. Adamec E, Vonsattel JP, Nixon RA. DNA strand breaks in Alzheimer's disease. Brain Res. 1999;849(1–2):67–77
  3. Ahlskog JE, Uitti RJ, Low PA, Tyce GM, Nickander KK, Petersen RC, et al. No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease. Mov Disord. 1995;10(5):566–573
  4. Ahmed N, Ahmed U, Thornalley PJ, Hager K, Fleischer G, Munch G. Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer's disease and link to cognitive impairment. J Neurochem. 2005;92(2):255–263
  5. Aisen PS, Davis KL, Berg JD, Schafer K, Campbell K, Thomas RG, et al. A randomized controlled trial of prednisone in Alzheimer's disease. Alzheimer's Disease Cooperative Study. Neurology. 2000;54(3):588–593
  6. Aisen PS, Schmeidler J, Pasinetti GM. Randomized pilot study of nimesulide treatment in Alzheimer's disease. Neurology. 2002;58(7):1050–1054
  7. Aksenov M, Aksenova M, Butterfield DA, Markesbery WR. Oxidative modification of creatine kinase BB in Alzheimer's disease brain. J Neurochem. 2000;74(6):2520–2527
  8. Aksenov MY, Aksenova MV, Butterfield DA, Geddes JW, Markesbery WR. Protein oxidation in the brain in Alzheimer's disease. Neuroscience. 2001;103(2):373–383
  9. Aksenov MY, Aksenova MV, Carney JM, Butterfield DA. Oxidative modification of glutamine synthetase by amyloid β peptide. Free Radic Res. 1997;27(3):267–281
  10. Andersen JK. Oxidative stress in neurodegeneration: cause or consequence?. Nat Med. 2004;10(Suppl):S18–S25
  11. Anderson AJ, Stoltzner S, Lai F, Su J, Nixon RA. Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL. Neurobiol Aging. 2000;21(4):511–524
  12. Anekonda TS, Reddy PH. Can herbs provide a new generation of drugs for treating Alzheimer's disease?. Brain Res Brain Res Rev. 2005;50(2):361–376
  13. Ani C, Grantham-McGregor S, Muller D. Nutritional supplementation in Down syndrome: theoretical considerations and current status. Dev Med Child Neurol. 2000;42(3):207–213
  14. Anneren G, Gardner A, Lundin T. Increased glutathione peroxidase activity in erythrocytes in patients with Alzheimer's disease/senile dementia of Alzheimer's type. Acta Neurol Scand. 1986;73(6):586–589
  15. Anneren G, Gebre-Medhin M, Gustavson KH. Increased plasma and erythrocyte selenium concentrations but decreased erythrocyte glutathione peroxidase activity after selenium supplementation in children with Down syndrome. Acta Paediatr Scand. 1989;78(6):879–884
  16. Anneren KG, Epstein CJ. Lipid peroxidation and superoxide dismutase-1 and glutathione peroxidase activities in trisomy 16 fetal mice and human trisomy 21 fibroblasts. Pediatr Res. 1987;21(1):88–92
  17. Antila E, Nordberg UR, Syvaoja EL, Westermarck T. Selenium therapy in Down syndrome (DS): a theory and a clinical trial. Adv Exp Med Biol. 1990;264:183–186
  18. Aruoma OI, Bahorun T, Jen LS. Neuroprotection by bioactive components in medicinal and food plant extracts. Mutat Res. 2003;544(2–3):203–215
  19. Asahara H, Wistort PM, Bank JF, Bakerian RH, Cunningham RP. Purification and characterization of Escherichia coli endonuclease III from the cloned nth gene. Biochemistry. 1989;28(10):4444–4449
  20. Asthana S, Craft S, Baker LD, Raskind MA, Birnbaum RS, Lofgreen CP, et al. Cognitive and neuroendocrine response to transdermal estrogen in postmenopausal women with Alzheimer's disease: results of a placebo-controlled, double-blind, pilot study. Psychoneuroendocrinology. 1999;24(6):657–677
  21. Baggot PJ, Eliseo AJ, Kalamarides JA, Shoemaker JD. A folate-dependent metabolite in amniotic fluid from pregnancies with normal or trisomy 21 chromosomes. Fetal Diagn Ther. 2006;21(1):148–152
  22. Balcz B, Kirchner L, Cairns N, Fountoulakis M, Lubec G. Increased brain protein levels of carbonyl reductase and alcohol dehydrogenase in Down syndrome and Alzheimer's disease. J Neural Transmemb. 2001;61(Suppl):193–201
  23. Baldereschi M, Di Carlo A, Lepore V, Bracco L, Maggi S, Grigoletto F, et al. Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging. Neurology. 1998;50(4):996–1002
  24. Baranano DE, Snyder SH. Neural roles for heme oxygenase: contrasts to nitric oxide synthase. Proc Natl Acad Sci USA. 2001;98(20):10996–11002
  25. Barenfeld LS, Pleskach NM, Bildin VN, Prokofjeva VV, Mikhelson VM. Radioresistant DNA synthesis in cells of patients showing increased chromosomal sensitivity to ionizing radiation. Mutat Res. 1986;165(3):159–164
  26. Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease animal models. J Alzheimers Dis. 2004;6(4):367–377
  27. Behl C, Skutella T, Lezoualc’h F, Post A, Widmann M, Newton CJ, et al. Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Mol Pharmacol. 1997;51(4):535–541
  28. Behl C, Widmann M, Trapp T, Holsboer F. 17-β Estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochem Biophys Res Commun. 1995;216(2):473–482
  29. Bennett FC, McClelland S, Kriegsmann EA, Andrus LB, Sells CJ. Vitamin and mineral supplementation in Down's syndrome. Pediatrics. 1983;72(5):707–713
  30. Benzi G, Moretti A. Are reactive oxygen species involved in Alzheimer's disease?. Neurobiol Aging. 1995;16(4):661–674
  31. Bermejo P, Gomez-Serranillos P, Santos J, Pastor E, Gil P, Martin-Aragon S. Determination of malonaldehyde in Alzheimer's disease: a comparative study of high-performance liquid chromatography and thiobarbituric acid test. Gerontology. 1997;43(4):218–222
  32. Bianchetti A, Rozzini R, Trabucchi M. Effects of acetyl-l-carnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors. Curr Med Res Opin. 2003;19(4):350–353
  33. Bidder RT, Gray P, Newcombe RG, Evans BK, Hughes M. The effects of multivitamins and minerals on children with Down syndrome. Dev Med Child Neurol. 1989;31(4):532–537
  34. Birks J, Flicker L. Selegiline for Alzheimer's disease. Cochrane Database Syst Rev. 2003;(1):CD000442
  35. Birks J, Grimley EV, Van Dongen M. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev. 2002;(4):CD003120
  36. Boiteux S, Gajewski E, Laval J, Dizdaroglu M. Substrate specificity of the Escherichia coli Fpg protein (formamidopyrimidine–DNA glycosylase): excision of purine lesions in DNA produced by ionizing radiation or photosensitization. Biochemistry. 1992;31(1):106–110
  37. Boothby LA, Doering PL. Vitamin C and Vitamin E for Alzheimer's disease. Ann Pharmacother. 2005;39(12):2073–2079
  38. Bourdel-Marchasson I, Delmas-Beauvieux MC, Peuchant E, Richard-Harston S, Decamps A, Reignier B, et al. Antioxidant defences and oxidative stress markers in erythrocytes and plasma from normally nourished elderly Alzheimer patients. Age Ageing. 2001;30(3):235–241
  39. Boyd-Kimball D, Sultana R, Abdul HM, Butterfield DA. Gamma-glutamylcysteine ethyl ester-induced up-regulation of glutathione protects neurons against Aβ(1–42)-mediated oxidative stress and neurotoxicity: implications for Alzheimer's disease. J Neurosci Res. 2005;79(5):700–706
  40. Bragin V, Chemodanova M, Dzhafarova N, Bragin I, Czerniawski JL, Aliev G. Integrated treatment approach improves cognitive function in demented and clinically depressed patients. Am J Alzheimers Dis Other Demen. 2005;20(1):21–26
  41. Bras A, Monteiro C, Rueff J. Oxidative stress in trisomy 21. A possible role in cataractogenesis. Ophthalmic Paediatr Genet. 1989;10(4):271–277
  42. Breitner JC, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, et al. Delayed onset of Alzheimer's disease with non-steroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging. 1995;16(4):523–530
  43. Brooksbank BW, Balazs R. Superoxide dismutase, glutathione peroxidase and lipoperoxidation in Down's syndrome fetal brain. Brain Res. 1984;318(1):37–44
  44. Brown RC, Han Z, Cascio C, Papadopoulos V. Oxidative stress-mediated DHEA formation in Alzheimer's disease pathology. Neurobiol Aging. 2003;24(1):57–65
  45. Brugge K, Nichols S, Saitoh T, Trauner D. Correlations of glutathione peroxidase activity with memory impairment in adults with Down syndrome. Biol Psychiatry. 1999;46(12):1682–1689
  46. Buckland P, Tidmarsh S, Spurlock G, Kaiser F, Yates M, O’Mahony G, et al. Amyloid precursor protein mRNA levels in the mononuclear blood cells of Alzheimer's and Down's patients. Brain Res Mol Brain Res. 1993;18(4):316–320
  47. Burke WJ, Roccaforte WH, Wengel SP, Bayer BL, Ranno AE, Willcockson NK. l-Deprenyl in the treatment of mild dementia of the Alzheimer type: results of a 15-month trial. J Am Geriatr Soc. 1993;41(11):1219–1225
  48. Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H, et al. Altered metabolism of the amyloid β precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron. 2002;33(5):677–688
  49. Busciglio J, Yankner BA. Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro. Nature. 1995;378(6559):776–779
  50. Bush A, Beail N. Risk factors for dementia in people with down syndrome: issues in assessment and diagnosis. Am J Ment Retard. 2004;109(2):83–97
  51. Butterfield D, Castegna A, Pocernich C, Drake J, Scapagnini G, Calabrese V. Nutritional approaches to combat oxidative stress in Alzheimer's disease. J Nutr Biochem. 2002;13(8):444–461
  52. Butterfield DA. Beta-amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimer's disease. Chem Res Toxicol. 1997;10(5):495–506
  53. Butterfield DA, Boyd-Kimball D, Castegna A. Proteomics in Alzheimer's disease: insights into potential mechanisms of neurodegeneration. J Neurochem. 2003;86(6):1313–1327
  54. Butterfield DA, Bush AI. Alzheimer's amyloid beta-peptide (1–42): involvement of methionine residue 35 in the oxidative stress and neurotoxicity properties of this peptide. Neurobiol Aging. 2004;25(5):563–568
  55. Butterfield DA, Castegna A, Lauderback CM, Drake J. Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. Neurobiol Aging. 2002;23(5):655–664
  56. Butterfield DA, Hensley K, Cole P, Subramaniam R, Aksenov M, Aksenova M, et al. Oxidatively induced structural alteration of glutamine synthetase assessed by analysis of spin label incorporation kinetics: relevance to Alzheimer's disease. J Neurochem. 1997;68(6):2451–2457
  57. Butterfield DA, Howard BJ, Yatin S, Allen KL, Carney JM. Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci USA. 1997;94(2):674–678
  58. Butterfield DA, Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev. 2001;122(9):945–962
  59. Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med. 2002;32(11):1050–1060
  60. Calabrese V, Boyd-Kimball D, Scapagnini G, Butterfield DA. Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: the role of vitagenes. In Vivo. 2004;18(3):245–267
  61. Calabrese V, Ravagna A, Colombrita C, Scapagnini G, Guagliano E, Calvani M, et al. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J Neurosci Res. 2005;79(4):509–521
  62. Calabrese V, Scapagnini G, Ravagna A, Colombrita C, Spadaro F, Butterfield DA, et al. Increased expression of heat shock proteins in rat brain during aging: relationship with mitochondrial function and glutathione redox state. Mech Ageing Dev. 2004;125(4):325–335
  63. Calabrese V, Stella AM, Butterfield DA, Scapagnini G. Redox regulation in neurodegeneration and longevity: role of the heme oxygenase and HSP70 systems in brain stress tolerance. Antioxid Redox Signal. 2004;6(5):895–913
  64. Calabrese V, Stella AM, Calvani M, Butterfield DA. Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. J Nutr Biochem. 2006;17(2):73–88
  65. Camandola S, Poli G, Mattson MP. The lipid peroxidation product 4-hydroxy-2,3-nonenal inhibits constitutive and inducible activity of nuclear factor kappa B in neurons. Brain Res Mol Brain Res. 2000;85(1–2):53–60
  66. Cameron DR, Braunstein GD. The use of dehydroepiandrosterone therapy in clinical practice. Treat Endocrinol. 2005;4(2):95–114
  67. Capone GT. Down syndrome: advances in molecular biology and the neurosciences. J Dev Behav Pediatr. 2001;22(1):40–59
  68. Cardoso SM, Proenca MT, Santos S, Santana I, Oliveira CR. Cytochrome c oxidase is decreased in Alzheimer's disease platelets. Neurobiol Aging. 2004;25(1):105–110
  69. Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I. Creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med. 2002;33(4):562–571
  70. Castegna A, Aksenov M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II. Dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem. 2002;82(6):1524–1532
  71. Cattabeni F, Colciaghi F, Di Luca M. Platelets provide human tissue to unravel pathogenic mechanisms of Alzheimer disease. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(5):763–770
  72. Ceballos-Picot I, Merad-Boudia M, Nicole A, Thevenin M, Hellier G, Legrain S, et al. Peripheral antioxidant enzyme activities and selenium in elderly subjects and in dementia of Alzheimer's type—place of the extracellular glutathione peroxidase. Free Radic Biol Med. 1996;20(4):579–587
  73. Cecchi C, Fiorillo C, Sorbi S, Latorraca S, Nacmias B, Bagnoli S, et al. Oxidative stress and reduced antioxidant defenses in peripheral cells from familial Alzheimer's patients. Free Radic Biol Med. 2002;33(10):1372–1379
  74. Chaney MO, Stine WB, Kokjohn TA, Kuo YM, Esh C, Rahman A, et al. RAGE and amyloid β interactions: atomic force microscopy and molecular modeling. Biochim Biophys Acta. 2005;1741(1–2):199–205
  75. Cheon MS, Shim KS, Kim SH, Hara A, Lubec G. Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part IV). Amino Acids. 2003;25(1):41–47
  76. Cherubini A, Martin A, Andres-Lacueva C, Di Iorio A, Lamponi M, Mecocci P, et al. Vitamin E levels, cognitive impairment and dementia in older persons: the InCHIANTI study. Neurobiol Aging. 2005;26(7):987–994
  77. Chiueh CC. Neuroprotective properties of nitric oxide. Ann NY Acad Sci. 1999;890:301–311
  78. Choi J, Malakowsky CA, Talent JM, Conrad CC, Gracy RW. Identification of oxidized plasma proteins in Alzheimer's disease. Biochem Biophys Res Commun. 2002;293(5):1566–1570
  79. Choi J, Rees HD, Weintraub ST, Levey AI, Chin LS, Li L. Oxidative modifications and aggregation of Cu, Zn-superoxide dismutase associated with Alzheimer and Parkinson diseases. J Biol Chem. 2005;280(12):11648–11655
  80. Christen Y. Oxidative stress and Alzheimer disease. Am J Clin Nutr. 2000;71(2):621S–629S
  81. Clarke R, Harrison G, Richards S. Effect of vitamins and aspirin on markers of platelet activation, oxidative stress and homocysteine in people at high risk of dementia. J Intern Med. 2003;254(1):67–75
  82. Colciaghi F, Marcello E, Borroni B, Zimmermann M, Caltagirone C, Cattabeni F, et al. Platelet APP, ADAM 10 and BACE alterations in the early stages of Alzheimer disease. Neurology. 2004;62(3):498–501
  83. Collins AR. Oxidative DNA damage, antioxidants, and cancer. Bioessays. 1999;21(3):238–246
  84. Colurso GJ, Nilson JE, Vervoort LG. Quantitative assessment of DNA fragmentation and β-amyloid deposition in insular cortex and midfrontal gyrus from patients with Alzheimer's disease. Life Sci. 2003;73(14):1795–1803
  85. Craft NE, Haitema TB, Garnett KM, Fitch KA, Dorey CK. Carotenoid, tocopherol, and retinol concentrations in elderly human brain. J Nutr Health Aging. 2004;8(3):156–162
  86. Croisile B, Trillet M, Fondarai J, Laurent B, Mauguiere F, Billardon M. Long-term and high-dose piracetam treatment of Alzheimer's disease. Neurology. 1993;43(2):301–305
  87. Crosti N, Bajer J, Gentile M, Resta G, Serra A. Catalase and glutathione peroxidase activity in cells with trisomy 21. Clin Genet. 1989;36(2):107–116
  88. Cummings BJ. Plaques and tangles: searching for primary events in a forest of data. Neurobiol Aging. 1997;18(4):358–362
  89. Davydov V, Hansen LA, Shackelford DA. Is DNA repair compromised in Alzheimer's disease?. Neurobiol Aging. 2003;24(7):953–968
  90. Dawson VL, Dawson TM. Nitric oxide in neurodegeneration. Prog Brain Res. 1998;118:215–229
  91. De Falco FA, D’Angelo E, Grimaldi G, Scafuro F, Sachez F, Caruso G. Effect of the chronic treatment with l-acetylcarnitine in Down's syndrome. Clin Ter. 1994;144(2):123–127
  92. de Haan JB, Cristiano F, Iannello RC, Kola I. Cu/Zn-superoxide dismutase and glutathione peroxidase during aging. Biochem Mol Biol Int. 1995;35(6):1281–1297
  93. de la Monte SM, Luong T, Neely TR, Robinson D, Wands JR. Mitochondrial DNA damage as a mechanism of cell loss in Alzheimer's disease. Lab Invest. 2000;80(8):1323–1335
  94. de las CN, Munoz U, Hermida OG, Martin-Requero A. Altered transcriptional regulators in response to serum in immortalized lymphocytes from Alzheimer's disease patients. Neurobiol Aging. 2005;26(5):615–624
  95. De Meyer GR, De Cleen DM, Cooper S, Knaapen MW, Jans DM, Martinet W, et al. Platelet phagocytosis and processing of β-amyloid precursor protein as a mechanism of macrophage activation in atherosclerosis. Circ Res. 2002;90(11):1197–1204
  96. DeFeudis FV, Papadopoulos V, Drieu K. Ginkgo biloba extracts and cancer: a research area in its infancy. Fundam Clin Pharmacol. 2003;17(4):405–417
  97. Deng J, Zhou DH, Li J, John WY, Gao C, Chen M. A 2-year follow-up study of alcohol consumption and risk of dementia. Clin Neurol Neurosurg. 2005;
  98. Di Luca M, Pastorino L, Bianchetti A, Perez J, Vignolo LA, Lenzi GL, et al. Differential level of platelet amyloid β precursor protein isoforms: an early marker for Alzheimer disease. Arch Neurol. 1998;55(9):1195–1200
  99. Di Luca M, Pastorino L, Cattabeni F, Zanardi R, Scarone S, Racagni G, et al. Abnormal pattern of platelet APP isoforms in Alzheimer disease and Down syndrome. Arch Neurol. 1996;53(11):1162–1166
  100. Dizdaroglu M. Oxidative damage to DNA in mammalian chromatin. Mutat Res. 1992;275(3–6):331–342
  101. Donfrancesco R, Dell’uomo A. Ginkgo biloba in Down syndrome. Phytomedicine. 2004;11(6):469
  102. Doody RS, Stevens JC, Beck C, Dubinsky RM, Kaye JA, Gwyther L, et al. Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1154–1166
  103. Drake J, Kanski J, Varadarajan S, Tsoras M, Butterfield DA. Elevation of brain glutathione by gamma-glutamylcysteine ethyl ester protects against peroxynitrite-induced oxidative stress. J Neurosci Res. 2002;68(6):776–784
  104. Drake J, Petroze R, Castegna A, Ding Q, Keller JN, Markesbery WR, et al. 4-Hydroxynonenal oxidatively modifies histones: implications for Alzheimer's disease. Neurosci Lett. 2004;356(3):155–158
  105. Druzhyna N, Nair RG, LeDoux SP, Wilson GL. Defective repair of oxidative damage in mitochondrial DNA in Down's syndrome. Mutat Res. 1998;409(2):81–89
  106. Du YS, Zhu H, Fu J, Yan SF, Roher A, Tourtellotte WW, et al. Amyloid-β peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc Natl Acad Sci USA. 1997;94(10):5296–5301
  107. Ellinson M, Thomas J, Patterson A. A critical evaluation of the relationship between serum Vitamin B, folate and total homocysteine with cognitive impairment in the elderly. J Hum Nutr Diet. 2004;17(4):371–383
  108. Engelhart MJ, Geerlings MI, Ruitenberg A, van Swieten JC, Hofman A, Witteman JC, et al. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002;287(24):3223–3229
  109. Engelhart MJ, Ruitenberg A, Meijer J, Kiliaan A, van Swieten JC, Hofman A, et al. Plasma levels of antioxidants are not associated with Alzheimer's disease or cognitive decline. Dement Geriatr Cogn Disord. 2005;19(2–3):134–139
  110. Engidawork E, Balic N, Juranville JF, Fountoulakis M, Dierssen M, Lubec G. Unaltered expression of Fas (CD95/APO-1), caspase-3, Bcl-2 and annexins in brains of fetal Down syndrome: evidence against increased apoptosis. J Neural Transm. 2001;61(Suppl):149–162
  111. Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: systematic review and meta-analysis of observational studies. BMJ. 2003;327(7407):128–132
  112. Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, Eyerman E, et al. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem. 2003;84(5):1173–1183
  113. Feng Z, Chang Y, Cheng Y, Zhang BL, Qu ZW, Qin C, et al. Melatonin alleviates behavioral deficits associated with apoptosis and cholinergic system dysfunction in the APP 695 transgenic mouse model of Alzheimer's disease. J Pineal Res. 2004;37(2):129–136
  114. Filip V, Kolibas E. Selegiline in the treatment of Alzheimer's disease: a long-term randomized placebo-controlled trial. Czech and Slovak Senile Dementia of Alzheimer Type Study Group. J Psychiatry Neurosci. 1999;24(3):234–243
  115. Fillenbaum GG, Kuchibhatla MN, Hanlon JT, Artz MB, Pieper CF, Schmader KE, et al. Dementia and Alzheimer's Disease in Community-Dwelling Elders Taking Vitamin C and/or Vitamin E. Ann Pharmacother. 2005;39(12):2009–2014
  116. Fillon-Emery N, Chango A, Mircher C, Barbe F, Blehaut H, Herbeth B, et al. Homocysteine concentrations in adults with trisomy 21: effect of B vitamins and genetic polymorphisms. Am J Clin Nutr. 2004;80(6):1551–1557
  117. Flicker L, Grimley EG. Piracetam for dementia or cognitive impairment. Cochrane Database Syst Rev. 2001;(2):CD001011
  118. Folin M, Baiguera S, Conconi MT, Pati T, Grandi C, Parnigotto PP, et al. The impact of risk factors of Alzheimer's disease in the Down syndrome. Int J Mol Med. 2003;11(2):267–270
  119. Fourrier A, Letenneur L, Begaud B, Dartigues JF. Non-steroidal antiinflammatory drug use and cognitive function in the elderly: inconclusive results from a population-based cohort study. J Clin Epidemiol. 1996;49(10):1201
  120. Freedman M, Rewilak D, Xerri T, Cohen S, Gordon AS, Shandling M, et al. l-Deprenyl in Alzheimer's disease: cognitive and behavioral effects. Neurology. 1998;50(3):660–668
  121. Gabbita SP, Lovell MA, Markesbery WR. Increased nuclear DNA oxidation in the brain in Alzheimer's disease. J Neurochem. 1998;71(5):2034–2040
  122. Gabryel B, Trzeciak HI. Nootropics: pharmacological properties and therapeutic use. Pol J Pharmacol. 1994;46(5):383–394
  123. Gadhia P, Gadhia M, Zankl H. Effects of bleomycin on Down's syndrome lymphocytes in culture. Mutat Res. 1988;207(3–4):153–158
  124. Gadhia P, Gadhia M, Zankl H. Adriamycin-induced sister chromatid exchange and chromosomal aberrations in Down's syndrome lymphocytes. Mutagenesis. 1991;6(1):31–33
  125. Gale CR, Martyn CN, Cooper C. Cognitive impairment and mortality in a cohort of elderly people. BMJ. 1996;312(7031):608–611
  126. Ganguli M, Chandra V, Kamboh MI, Johnston JM, Dodge HH, Thelma BK, et al. Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study. Arch Neurol. 2000;57(6):824–830
  127. Garcia A, Zanibbi K. Homocysteine and cognitive function in elderly people. CMAJ. 2004;171(8):897–904
  128. Genedani S, Rasio G, Cortelli P, Antonelli F, Guidolin D, Galantucci M, et al. Studies on homocysteine and dehydroepiandrosterone sulphate plasma levels in Alzheimer's disease patients and in Parkinson's disease patients. Neurotox Res. 2004;6(4):327–332
  129. Gibbs RB. Estrogen and nerve growth factor-related systems in brain. Effects on basal forebrain cholinergic neurons and implications for learning and memory processes and aging. Ann NY Acad Sci. 1994;743:165–196
  130. Gillman MW, Cupples LA, Gagnon D, Posner BM, Ellison RC, Castelli WP, et al. Protective effect of fruits and vegetables on development of stroke in men. JAMA. 1995;273(14):1113–1117
  131. Girones X, Guimera A, Cruz-Sanchez CZ, Ortega A, Sasaki N, Makita Z, et al. N epsilon-carboxymethyllysine in brain aging, diabetes mellitus, and Alzheimer's disease. Free Radic Biol Med. 2004;36(10):1241–1247
  132. Good PF, Werner P, Hsu A, Olanow CW, Perl DP. Evidence of neuronal oxidative damage in Alzheimer's disease. Am J Pathol. 1996;149(1):21–28
  133. Govoni S, Bergamaschi S, Gasparini L, Quaglia C, Racchi M, Cattaneo E, et al. Fibroblasts of patients affected by Down's syndrome oversecrete amyloid precursor protein and are hyporesponsive to protein kinase C stimulation. Neurology. 1996;47(4):1069–1075
  134. Gromadzinska J, Wasowicz W, Sklodowska M, Strozynski H. Glutathione peroxidase activity, lipid peroxides and selenium status in blood in patients with Down's syndrome. J Clin Chem Clin Biochem. 1988;26(5):255–258
  135. Growdon JH, Corkin S, Huff FJ, Rosen TJ. Piracetam combined with lecithin in the treatment of Alzheimer's disease. Neurobiol Aging. 1986;7(4):269–276
  136. Gsell W, Conrad R, Hickethier M, Sofic E, Frolich L, Wichart I, et al. Decreased catalase activity but unchanged superoxide dismutase activity in brains of patients with dementia of Alzheimer type. J Neurochem. 1995;64(3):1216–1223
  137. Gualandri W, Gualandri L, Demartini G, Esposti R, Marthyn P, Volonte S, et al. Redox balance in patients with Down's syndrome before and after dietary supplementation with alpha-lipoic acid and l-cysteine. Int J Clin Pharmacol Res. 2003;23(1):23–30
  138. Guidi I, Galimberti D, Lonati S, Novembrino C, Bamonti F, Tiriticco M, et al. Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2006;27(2):262–269
  139. Gulesserian T, Engidawork E, Fountoulakis M, Lubec G. Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome. J Neural Transm. 2001;61(Suppl):71–84
  140. Gulesserian T, Seidl R, Hardmeier R, Cairns N, Lubec G. Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome. J Investig Med. 2001;49(1):41–46
  141. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. 1995;41(12 Pt 2):1819–1828
  142. Hayn M, Kremser K, Singewald N, Cairns N, Nemethova M, Lubec B, et al. Evidence against the involvement of reactive oxygen species in the pathogenesis of neuronal death in Down's syndrome and Alzheimer's disease. Life Sci. 1996;59(7):537–544
  143. Head E, Garzon-Rodriguez W, Johnson JK, Lott IT, Cotman CW, Glabe C. Oxidation of Aβ and plaque biogenesis in Alzheimer's disease and Down syndrome. Neurobiol Dis. 2001;8(5):792–806
  144. Head E, Lott IT. Down syndrome and beta-amyloid deposition. Curr Opin Neurol. 2004;17(2):95–100
  145. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):23–33
  146. Hensley K, Hall N, Subramaniam R, Cole P, Harris M, Aksenov M, et al. Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J Neurochem. 1995;65(5):2146–2156
  147. Hensley K, Maidt ML, Yu Z, Sang H, Markesbery WR, Floyd RA. Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation. J Neurosci. 1998;18(20):8126–8132
  148. Hermon M, Cairns N, Egly JM, Fery A, Labudova O, Lubec G. Expression of DNA excision-repair-cross-complementing proteins p80 and p89 in brain of patients with Down syndrome and Alzheimer's disease. Neurosci Lett. 1998;251(1):45–48
  149. Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, et al. Mitochondrial abnormalities in Alzheimer's disease. J Neurosci. 2001;21(9):3017–3023
  150. Ho PI, Ashline D, Dhitavat S, Ortiz D, Collins SC, Shea TB, et al. Folate deprivation induces neurodegeneration: roles of oxidative stress and increased homocysteine. Neurobiol Dis. 2003;14(1):32–42
  151. Hogervorst E, Williams J, Budge M, Riedel W, Jolles J. The nature of the effect of female gonadal hormone replacement therapy on cognitive function in post-menopausal women: a meta-analysis. Neuroscience. 2000;101(3):485–512
  152. Hogervorst E, Williams J, Combrinck M, David SA. Measuring serum oestradiol in women with Alzheimer's disease: the importance of the sensitivity of the assay method. Eur J Endocrinol. 2003;148(1):67–72
  153. Hopkins WE, Fukagawa NK, Sobel BE, Schneider DJ. Plasminogen activator inhibitor type 1 in adults with Down syndrome and protection against macrovascular disease. Am J Cardiol. 2000;85(6):784–786
  154. Howes MJ, Houghton PJ. Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function. Pharmacol Biochem Behav. 2003;75(3):513–527
  155. Hudson S, Tabet N. Acetyl-l-carnitine for dementia. Cochrane Database Syst Rev. 2003;(2):CD003158
  156. in t’ Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, et al. Non-steroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med. 2001;345(21):1515–1521
  157. Isacson O, Seo H, Lin L, Albeck D, Granholm AC. Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh. Trends Neurosci. 2002;25(2):79–84
  158. Iwatsubo T, Mann DM, Odaka A, Suzuki N, Ihara Y. Amyloid beta protein (A beta) deposition: A beta 42(43) precedes A beta 40 in Down syndrome. Ann Neurol. 1995;37(3):294–299
  159. Jaffe AB, Toran-Allerand CD, Greengard P, Gandy SE. Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. J Biol Chem. 1994;269(18):13065–13068
  160. Jansen S, Duncan V, Morgan D. Melatonin for cognitive impairment. Cochrane Database Syst Rev. 2006;(1):CD003802
  161. Joseph JA, Shukitt-Hale B, Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr. 2005;81(1 Suppl):313S–316S
  162. Joshi G, Perluigi M, Sultana R, Agrippino R, Calabrese V, Butterfield DA. In vivo protection of synaptosomes by ferulic acid ethyl ester (FAEE) from oxidative stress mediated by 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH) or Fe(2+)/H(2)O(2): Insight into mechanisms of neuroprotection and relevance to oxidative stress-related neurodegenerative disorders. Neurochem Int. 2006;48(4):318–327
  163. Jovanovic SV, Clements D, MacLeod K. Biomarkers of oxidative stress are significantly elevated in Down syndrome. Free Radic Biol Med. 1998;25(9):1044–1048
  164. Kadioglu E, Sardas S, Aslan S, Isik E, Esat KA. Detection of oxidative DNA damage in lymphocytes of patients with Alzheimer's disease. Biomarkers. 2004;9(2):203–209
  165. Kalman J, Dey I, Ilona SV, Matkovics B, Brown D, Janka Z, et al. Platelet membrane fluidity and plasma malondialdehyde levels in Alzheimer's demented patients with and without family history of dementia. Biol Psychiatry. 1994;35(3):190–194
  166. Kanowski S, Herrmann WM, Stephan K, Wierich W, Horr R. Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry. 1996;29(2):47–56
  167. Kanowski S, Hoerr R. Ginkgo biloba extract EGb 761 in dementia: intent-to-treat analyses of a 24-week, multi-center, double-blind, placebo-controlled, randomized trial. Pharmacopsychiatry. 2003;36(6):297–303
  168. Karelson E, Bogdanovic N, Garlind A, Winblad B, Zilmer K, Kullisaar T, et al. The cerebrocortical areas in normal brain aging and in Alzheimer's disease: noticeable differences in the lipid peroxidation level and in antioxidant defense. Neurochem Res. 2001;26(4):353–361
  169. Kawamoto EM, Munhoz CD, Glezer I, Bahia VS, Caramelli P, Nitrini R, et al. Oxidative state in platelets and erythrocytes in aging and Alzheimer's disease. Neurobiol Aging. 2005;26(6):857–864
  170. Kelloff GJ, Crowell JA, Steele VE, Lubet RA, Malone WA, Boone CW, et al. Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. J Nutr. 2000;130(2S Suppl):467S–471S
  171. Kim SH, Vlkolinsky R, Cairns N, Lubec G. Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer's disease and Down syndrome. Cell Mol Life Sci. 2000;57(12):1810–1816
  172. Kirsch M, De Groot H. NAD(P)H, a directly operating antioxidant?. FASEB J. 2001;15(9):1569–1574
  173. Korenberg JR, Kawashima H, Pulst SM, Ikeuchi T, Ogasawara N, Yamamoto K, et al. Molecular definition of a region of chromosome 21 that causes features of the Down syndrome phenotype. Am J Hum Genet. 1990;47(2):236–246
  174. Krasuski JS, Alexander GE, Horwitz B, Rapoport SI, Schapiro MB. Relation of medial temporal lobe volumes to age and memory function in non-demented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease. Am J Psychiatry. 2002;159(1):74–81
  175. Kuo HK, Sorond FA, Chen JH, Hashmi A, Milberg WP, Lipsitz LA. The role of homocysteine in multisystem age-related problems: a systematic review. J Gerontol A Biol Sci Med Sci. 2005;60(9):1190–1201
  176. Kurobe N, Suzuki F, Okajima K, Kato K. Sensitive enzyme immunoassay for human Cu/Zn superoxide dismutase. Clin Chim Acta. 1990;187(1):11–20
  177. Lambert B, Hansson K, Bui TH, Funes-Cravioto F, Lindsten J. DNA repair and frequency of X-ray and UV-light induced chromosome aberrations in leukocytes from patients with Down's syndrome. Ann Hum Genet. 1976;39(3):293–303
  178. Laurin D, Masaki KH, Foley DJ, White LR, Launer LJ. Midlife dietary intake of antioxidants and risk of late-life incident dementia: the Honolulu-Asia Aging Study. Am J Epidemiol. 2004;159(10):959–967
  179. Le Bars PL. Response patterns of EGb 761 in Alzheimer's disease: influence of neuropsychological profiles. Pharmacopsychiatry. 2003;36(Suppl 1):S50–S55
  180. Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA. 1997;278(16):1327–1332
  181. Le Bars PL, Velasco FM, Ferguson JM, Dessain EC, Kieser M, Hoerr R. Influence of the severity of cognitive impairment on the effect of the Ginkgo biloba extract EGb 761 in Alzheimer's disease. Neuropsychobiology. 2002;45(1):19–26
  182. Leboeuf R. Homocysteine and Alzheimer's disease. J Am Diet Assoc. 2003;103(3):304–307
  183. Ledesma MD, Bonay P, Colaco C, Avila J. Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem. 1994;269(34):21614–21619
  184. Leonard JC, Merz T. Repair of single-strand breaks in normal and trisomic lymphocytes. Mutat Res. 1982;105(6):417–422
  185. Leverenz JB, Raskind MA. Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Exp Neurol. 1998;150(2):296–304
  186. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001;21(21):8370–8377
  187. Liu H, Harrell LE, Shenvi S, Hagen T, Liu RM. Gender differences in glutathione metabolism in Alzheimer's disease. J Neurosci Res. 2005;79(6):861–867
  188. Liu J, Ames BN. Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer's disease, and Parkinson's disease. Nutr Neurosci. 2005;8(2):67–89
  189. Liu RH. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr. 2003;78(3 Suppl):517S–520S
  190. Lobaugh NJ, Karaskov V, Rombough V, Rovet J, Bryson S, Greenbaum R, et al. Piracetam therapy does not enhance cognitive functioning in children with down syndrome. Arch Pediatr Adolesc Med. 2001;155(4):442–448
  191. Lott IT, Head E. Alzheimer disease and Down syndrome: factors in pathogenesis. Neurobiol Aging. 2005;26(3):383–389
  192. Lovell MA, Ehmann WD, Butler SM, Markesbery WR. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease. Neurology. 1995;45(8):1594–1601
  193. Lovell MA, Gabbita SP, Markesbery WR. Increased DNA oxidation and decreased levels of repair products in Alzheimer's disease ventricular CSF. J Neurochem. 1999;72(2):771–776
  194. Lovell MA, Xie C, Markesbery WR. Decreased base excision repair and increased helicase activity in Alzheimer's disease brain. Brain Res. 2000;855(1):116–123
  195. Lovell MA, Xie C, Xiong S, Markesbery WR. Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. J Alzheimers Dis. 2003;5(3):229–239
  196. Luchsinger JA, Mayeux R. Dietary factors and Alzheimer's disease. Lancet Neurol. 2004;3(10):579–587
  197. Luchsinger JA, Tang MX, Shea S, Mayeux R. Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol. 2003;60(2):203–208
  198. Luchsinger JA, Tang MX, Siddiqui M, Shea S, Mayeux R. Alcohol intake and risk of dementia. J Am Geriatr Soc. 2004;52(4):540–546
  199. Lyras L, Cairns NJ, Jenner A, Jenner P, Halliwell B. An assessment of oxidative damage to proteins, lipids, and DNA in brain from patients with Alzheimer's disease. J Neurochem. 1997;68(5):2061–2069
  200. Maki PM, Resnick SM. Effects of estrogen on patterns of brain activity at rest and during cognitive activity: a review of neuroimaging studies. Neuroimage. 2001;14(4):789–801
  201. Malaguarnera M, Ferri R, Bella R, Alagona G, Carnemolla A, Pennisi G. Homocysteine, Vitamin B12 and folate in vascular dementia and in Alzheimer disease. Clin Chem Lab Med. 2004;42(9):1032–1035
  202. Malouf M, Grimley EJ, Areosa SA. Folic acid with or without Vitamin B12 for cognition and dementia. Cochrane Database Syst Rev. 2003;(4):CD004514
  203. Malouf R, Areosa SA. Vitamin B12 for cognition. Cochrane Database Syst Rev. 2003;(3):CD004326
  204. Malouf R, Grimley EJ. The effect of Vitamin B6 on cognition. Cochrane Database Syst Rev. 2003;(4):CD004393
  205. Maluf SW, Erdtmann B. Genomic instability in Down syndrome and Fanconi anemia assessed by micronucleus analysis and single-cell gel electrophoresis. Cancer Genet Cytogenet. 2001;124(1):71–75
  206. Marcus DL, Thomas C, Rodriguez C, Simberkoff K, Tsai JS, Strafaci JA, et al. Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer's disease. Exp Neurol. 1998;150(1):40–44
  207. Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 1997;23(1):134–147
  208. Markesbery WR, Lovell MA. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol Aging. 1998;19(1):33–36
  209. Martin-Aragon S, Benedi JM, Villar AM. Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment. J Pharm Pharmacol. 1997;49(1):49–52
  210. Martins RN, Muir J, Brooks WS, Creasey H, Montgomery P, Sellers P, et al. Plasma amyloid precursor protein is decreased in Alzheimer's disease. Neuroreport. 1993;4(6):757–759
  211. Mates JM, Perez-Gomez C, Nunez dC I. Antioxidant enzymes and human diseases. Clin Biochem. 1999;32(8):595–603
  212. Maxwell CJ, Hicks MS, Hogan DB, Basran J, Ebly EM. Supplemental use of antioxidant vitamins and subsequent risk of cognitive decline and dementia. Dement Geriatr Cogn Disord. 2005;20(1):45–51
  213. Mazeh D, Cholostoy A, Zemishlani C, Barak Y. Elderly psychiatric patients at risk of folic acid deficiency: a case controlled study. Arch Gerontol Geriatr. 2005;41(3):297–302
  214. McDaniel MA, Maier SF, Einstein GO. “Brain-specific” nutrients: a memory cure?. Nutrition. 2003;19(11–12):957–975
  215. Mecocci P, Polidori MC, Cherubini A, Ingegni T, Mattioli P, Catani M, et al. Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease. Arch Neurol. 2002;59(5):794–798
  216. Mecocci P, Polidori MC, Ingegni T, Cherubini A, Chionne F, Cecchetti R, et al. Oxidative damage to DNA in lymphocytes from AD patients. Neurology. 1998;51(4):1014–1017
  217. Mehta PD, Mehta SP, Fedor B, Patrick BA, Emmerling M, Dalton AJ. Plasma amyloid beta protein 1–42 levels are increased in old Down syndrome but not in young Down syndrome. Neurosci Lett. 2003;342(3):155–158
  218. Melaragno MI, Smith MA, Kormann-Bortolotto MH, Toniolo Neto JT. Lymphocyte proliferation and sister chromatid exchange in Alzheimer's disease. Gerontology. 1991;37(6):293–298
  219. Menendez M. Down syndrome, Alzheimer's disease and seizures. Brain Dev. 2005;27(4):246–252
  220. Midorikawa K, Kawanishi S. Superoxide dismutases enhance H2O2-induced DNA damage and alter its site specificity. FEBS Lett. 2001;495(3):187–190
  221. Migliore L, Fontana I, Colognato R, Coppede F, Siciliano G, Murri L. Searching for the role and the most suitable biomarkers of oxidative stress in Alzheimer's disease and in other neurodegenerative diseases. Neurobiol Aging. 2005;26(5):587–595
  222. Migliore L, Fontana I, Trippi F, Colognato R, Coppede F, Tognoni G, et al. Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients. Neurobiol Aging. 2005;26(5):567–573
  223. Miller JW, Green R, Mungas DM, Reed BR, Jagust WJ. Homocysteine, Vitamin B6, and vascular disease in AD patients. Neurology. 2002;58(10):1471–1475
  224. Misonou H, Morishima-Kawashima M, Ihara Y. Oxidative stress induces intracellular accumulation of amyloid beta-protein (Abeta) in human neuroblastoma cells. Biochemistry. 2000;39(23):6951–6959
  225. Miyata T, Inagi R, Asahi K, Yamada Y, Horie K, Sakai H, et al. Generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids. FEBS Lett. 1998;437(1–2):24–28
  226. Mizrahi EH, Jacobsen DW, Debanne SM, Traore F, Lerner AJ, Friedland RP, et al. Plasma total homocysteine levels, dietary Vitamin B6 and folate intake in AD and healthy aging. J Nutr Health Aging. 2003;7(3):160–165
  227. Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-l-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol. 2003;18(2):61–71
  228. Montine KS, Quinn JF, Zhang J, Fessel JP, Roberts LJ, Morrow JD, et al. Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases. Chem Phys Lipids. 2004;128(1–2):117–124
  229. Montine TJ, Quinn JF, Milatovic D, Silbert LC, Dang T, Sanchez S, et al. Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer's disease. Ann Neurol. 2002;52(2):175–179
  230. Moreira PI, Honda K, Zhu X, Nunomura A, Casadesus G, Smith MA, et al. Brain and brawn. Parallels in oxidative strength. Neurology. 2005;
  231. Morocz M, Kalman J, Juhasz A, Sinko I, McGlynn AP, Downes CS, et al. Elevated levels of oxidative DNA damage in lymphocytes from patients with Alzheimer's disease. Neurobiol Aging. 2002;23(1):47–53
  232. Morris MC, Evans DA, Bienias JL, Scherr PA, Tangney CC, Hebert LE, et al. Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline. J Neurol Neurosurg Psychiatry. 2004;75(8):1093–1099
  233. Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Aggarwal N, et al. Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA. 2002;287(24):3230–3237
  234. Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS, Aggarwal NT, et al. Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutr. 2005;81(2):508–514
  235. Mruthinti S, Buccafusco JJ, Hill WD, Waller JL, Jackson TW, Zamrini EY, et al. Autoimmunity in Alzheimer's disease: increased levels of circulating IgGs binding Abeta and RAGE peptides. Neurobiol Aging. 2004;25(8):1023–1032
  236. Muchova J, Sustrova M, Garaiova I, Liptakova A, Blazicek P, Kvasnicka P, et al. Influence of age on activities of antioxidant enzymes and lipid peroxidation products in erythrocytes and neutrophils of Down syndrome patients. Free Radic Biol Med. 2001;31(4):499–508
  237. Mukamal KJ, Kuller LH, Fitzpatrick AL, Longstreth WT, Mittleman MA, Siscovick DS. Prospective study of alcohol consumption and risk of dementia in older adults. JAMA. 2003;289(11):1405–1413
  238. Mullaart E, Boerrigter ME, Ravid R, Swaab DF, Vijg J. Increased levels of DNA breaks in cerebral cortex of Alzheimer's disease patients. Neurobiol Aging. 1990;11(3):169–173
  239. Mulnard RA, Corrada MM, Kawas CH. Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment. Curr Neurol Neurosci Rep. 2004;4(5):368–373
  240. Mulnard RA, Cotman CW, Kawas C, van Dyck CH, Sano M, Doody R, et al. Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study. JAMA. 2000;283(8):1007–1015
  241. Munch G, Kuhla B, Luth HJ, Arendt T, Robinson SR. Anti-ageing defences against Alzheimer's disease. Biochem Soc Trans. 2003;31(Pt 6):1397–1399
  242. Munch G, Thome J, Foley P, Schinzel R, Riederer P. Advanced glycation endproducts in ageing and Alzheimer's disease. Brain Res Brain Res Rev. 1997;23(1–2):134–143
  243. Nawata H, Yanase T, Goto K, Okabe T, Nomura M, Ashida K, et al. Adrenopause. Horm Res. 2004;62(Suppl 3):110–114
  244. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol. 2001;60(8):759–767
  245. Nunomura A, Perry G, Pappolla MA, Friedland RP, Hirai K, Chiba S, et al. Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. J Neuropathol Exp Neurol. 2000;59(11):1011–1017
  246. Nunomura A, Perry G, Pappolla MA, Wade R, Hirai K, Chiba S, et al. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. J Neurosci. 1999;19(6):1959–1964
  247. Odetti P, Angelini G, Dapino D, Zaccheo D, Garibaldi S, Dagna-Bricarelli F, et al. Early glycoxidation damage in brains from Down's syndrome. Biochem Biophys Res Commun. 1998;243(3):849–851
  248. Ohkura T, Isse K, Akazawa K, Hamamoto M, Yaoi Y, Hagino N. Long-term estrogen replacement therapy in female patients with dementia of the Alzheimer type: seven case reports. Dementia. 1995;6(2):99–107
  249. Okabe T, Hamaguchi K, Inafuku T, Hara M. Aging and superoxide dismutase activity in cerebrospinal fluid. J Neurol Sci. 1996;141(1–2):100–104
  250. Oken BS, Storzbach DM, Kaye JA. The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch Neurol. 1998;55(11):1409–1415
  251. Ono K, Hasegawa K, Naiki H, Yamada M. Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res. 2004;75(6):742–750
  252. Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M. Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro. Exp Neurol. 2004;189(2):380–392
  253. Padovani A, Borroni B, Colciaghi F, Pettenati C, Cottini E, Agosti C, et al. Abnormalities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairment and Alzheimer disease. Arch Neurol. 2002;59(1):71–75
  254. Paganini-Hill A, Henderson VW. Estrogen replacement therapy and risk of Alzheimer disease. Arch Intern Med. 1996;156(19):2213–2217
  255. Pallister C, Jung SS, Shaw I, Nalbantoglu J, Gauthier S, Cashman NR. Lymphocyte content of amyloid precursor protein is increased in Down's syndrome and aging. Neurobiol Aging. 1997;18(1):97–103
  256. Pastor MC, Sierra C, Dolade M, Navarro E, Brandi N, Cabre E, et al. Antioxidant enzymes and fatty acid status in erythrocytes of Down's syndrome patients. Clin Chem. 1998;44(5):924–929
  257. Pastore A, Tozzi G, Gaeta LM, Giannotti A, Bertini E, Federici G, et al. Glutathione metabolism and antioxidant enzymes in children with Down syndrome. J Pediatr. 2003;142(5):583–585
  258. Pelsman A, Hoyo-Vadillo C, Gudasheva TA, Seredenin SB, Ostrovskaya RU, Busciglio J. GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons. Int J Dev Neurosci. 2003;21(3):117–124
  259. Percy ME, Dalton AJ, Markovic VD, McLachlan DR, Hummel JT, Rusk AC, et al. Red cell superoxide dismutase, glutathione peroxidase and catalase in Down syndrome patients with and without manifestations of Alzheimer disease. Am J Med Genet. 1990;35(4):459–467
  260. Perrin R, Briancon S, Jeandel C, Artur Y, Minn A, Penin F, et al. Blood activity of Cu/Zn superoxide dismutase, glutathione peroxidase and catalase in Alzheimer's disease: a case-control study. Gerontology. 1990;36(5–6):306–313
  261. Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379–2388
  262. Petronis A. Alzheimer's disease and down syndrome: from meiosis to dementia. Exp Neurol. 1999;158(2):403–413
  263. Pincheira J, Navarrete MH, de la TC, Tapia G, Santos MJ. Effect of Vitamin E on chromosomal aberrations in lymphocytes from patients with Down's syndrome. Clin Genet. 1999;55(3):192–197
  264. Planas M, Conde M, Audivert S, Perez-Portabella C, Burgos R, Chacon P, et al. Micronutrient supplementation in mild Alzheimer disease patients. Clin Nutr. 2004;23(2):265–272
  265. Pocernich CB, Butterfield DA. Acrolein inhibits NADH-linked mitochondrial enzyme activity: implications for Alzheimer's disease. Neurotox Res. 2003;5(7):515–520
  266. Pogribna M, Melnyk S, Pogribny I, Chango A, Yi P, James SJ. Homocysteine metabolism in children with Down syndrome: in vitro modulation. Am J Hum Genet. 2001;69(1):88–95
  267. Poon HF, Farr SA, Thongboonkerd V, Lynn BC, Banks WA, Morley JE, et al. Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders. Neurochem Int. 2005;46(2):159–168
  268. Porstmann T, Wietschke R, Schmechta H, Grunow R, Porstmann B, Bleiber R, et al. A rapid and sensitive enzyme immunoassay for Cu/Zn superoxide dismutase with polyclonal and monoclonal antibodies. Clin Chim Acta. 1988;171(1):1–10
  269. Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR. Regional membrane phospholipid alterations in Alzheimer's disease. Neurochem Res. 1998;23(1):81–88
  270. Pratico D, Clark CM, Lee VM, Trojanowski JQ, Rokach J, FitzGerald GA. Increased 8,12-iso-iPF2alpha-VI in Alzheimer's disease: correlation of a non-invasive index of lipid peroxidation with disease severity. Ann Neurol. 2000;48(5):809–812
  271. Pratico D, Delanty N. Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. Am J Med. 2000;109(7):577–585
  272. Pratico D, Iuliano L, Amerio G, Tang LX, Rokach J, Sabatino G, et al. Down's syndrome is associated with increased 8,12-iso-iPF2alpha-VI levels: evidence for enhanced lipid peroxidation in vivo. Ann Neurol. 2000;48(5):795–798
  273. Pratico D, Lee VM, Trojanowski JQ, Rokach J, FitzGerald GA. Increased F2-isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo. FASEB J. 1998;12(15):1777–1783
  274. Pueschel SM, Craig WY, Haddow JE. Lipids and lipoproteins in persons with Down's syndrome. J Intellect Disabil Res. 1992;36(4):365–369
  275. Pulido R, Jimenez-Escrig A, Orensanz L, Saura-Calixto F, Jimenez-Escrig A. Study of plasma antioxidant status in Alzheimer's disease. Eur J Neurol. 2005;12(7):531–535
  276. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, et al. Homocysteine, folate, and Vitamin B12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am J Clin Nutr. 2004;80(1):114–122
  277. Raji NS, Rao KS. Trisomy 21 and accelerated aging: DNA-repair parameters in peripheral lymphocytes of Down's syndrome patients. Mech Ageing Dev. 1998;100(1):85–101
  278. Rebhorn H, Pfeiffenberger H. In vitro life span and “unscheduled DNA synthesis” in subconfluent cultures and clones of trisomic and normal diploid fibroblasts. Mech Ageing Dev. 1982;18(3):201–208
  279. Reddy VP, Obrenovich ME, Atwood CS, Perry G, Smith MA. Involvement of Maillard reactions in Alzheimer disease. Neurotox Res. 2002;4(3):191–209
  280. Reeves RH, Baxter LL, Richtsmeier JT. Too much of a good thing: mechanisms of gene action in Down syndrome. Trends Genet. 2001;17(2):83–88
  281. Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Meth Enzymol. 1994;233:357–363
  282. Richter T, Munch G, Luth HJ, Arendt T, Kientsch-Engel R, Stahl P, et al. Immunochemical crossreactivity of antibodies specific for “advanced glycation endproducts” with “advanced lipoxidation endproducts”. Neurobiol Aging. 2005;26(4):465–474
  283. Rinaldi P, Polidori MC, Metastasio A, Mariani E, Mattioli P, Cherubini A, et al. Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer's disease. Neurobiol Aging. 2003;24(7):915–919
  284. Ringman JM, Frautschy SA, Cole GM, Masterman DL, Cummings JL. A potential role of the curry spice curcumin in Alzheimer's disease. Curr Alzheimer Res. 2005;2(2):131–136
  285. Riviere S, Birlouez-Aragon I, Vellas B. Plasma protein glycation in Alzheimer's disease. Glycoconj J. 1998;15(10):1039–1042
  286. Roizen NJ, Patterson D. Down's syndrome. Lancet. 2003;361(9365):1281–1289
  287. Rosenberg RN, Baskin F, Fosmire JA, Risser R, Adams P, Svetlik D, et al. Altered amyloid protein processing in platelets of patients with Alzheimer disease. Arch Neurol. 1997;54(2):139–144
  288. Rosenblatt DS. Folate and homocysteine metabolism and gene polymorphisms in the etiology of Down syndrome. Am J Clin Nutr. 1999;70(4):429–430
  289. Ruitenberg A, van Swieten JC, Witteman JC, Mehta KM, van Duijn CM, Hofman A, et al. Alcohol consumption and risk of dementia: the Rotterdam Study. Lancet. 2002;359(9303):281–286
  290. Salerno-Kennedy R, Cashman KD. Relationship between dementia and nutrition-related factors and disorders: an overview. Int J Vitam Nutr Res. 2005;75(2):83–95
  291. Salman M. Systematic review of the effect of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome. Eur J Paediatr Neurol. 2002;6(4):213–219
  292. Sanij E, Hatzistavrou T, Hertzog P, Kola I, Wolvetang EJ. Ets-2 is induced by oxidative stress and sensitizes cells to H(2)O(2)-induced apoptosis: implications for Down's syndrome. Biochem Biophys Res Commun. 2001;287(4):1003–1008
  293. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997;336(17):1216–1222
  294. Sauer J, Tabet N, Howard R. Alpha lipoic acid for dementia. Cochrane Database Syst Rev. 2004;(1):CD004244
  295. Savaskan E, Olivieri G, Meier F, Seifritz E, Wirz-Justice A, Muller-Spahn F. Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity. Gerontology. 2003;49(6):380–383
  296. Sawa A, Oyama F, Cairns NJ, Amano N, Matsushita M. Aberrant expression of bcl-2 gene family in Down's syndrome brains. Brain Res Mol Brain Res. 1997;48(1):53–59
  297. Scapagnini G, Butterfield DA, Colombrita C, Sultana R, Pascale A, Calabrese V. Ethyl ferulate, a lipophilic polyphenol, induces HO-1 and protects rat neurons against oxidative stress. Antioxid Redox Signal. 2004;6(5):811–818
  298. Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer's disease. Neurology. 1999;53(1):197–201
  299. Schneider LS, DeKosky ST, Farlow MR, Tariot PN, Hoerr R, Kieser M. A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer's type. Curr Alzheimer Res. 2005;2(5):541–551
  300. Schneider LS, Pollock VE, Zemansky MF, Gleason RP, Palmer R, Sloane RB. A pilot study of low-dose l-deprenyl in Alzheimer's disease. J Geriatr Psychiatry Neurol. 1991;4(3):143–148
  301. Schuchmann S, Heinemann U. Increased mitochondrial superoxide generation in neurons from trisomy 16 mice: a model of Down's syndrome. Free Radic Biol Med. 2000;28(2):235–250
  302. Schuessel K, Leutner S, Cairns NJ, Muller WE, Eckert A. Impact of gender on upregulation of antioxidant defence mechanisms in Alzheimer's disease brain. J Neural Transmemb. 2004;111(9):1167–1182
  303. Schulz V. Ginkgo extract or cholinesterase inhibitors in patients with dementia: what clinical trials and guidelines fail to consider. Phytomedicine. 2003;10(Suppl 4):74–79
  304. Schupf N, Kapell D, Nightingale B, Rodriguez A, Tycko B, Mayeux R. Earlier onset of Alzheimer's disease in men with Down syndrome. Neurology. 1998;50(4):991–995
  305. Schupf N, Sergievsky GH. Genetic and host factors for dementia in Down's syndrome. Br J Psychiatry. 2002;180:405–410
  306. Seidl R, Greber S, Schuller E, Bernert G, Cairns N, Lubec G. Evidence against increased oxidative DNA-damage in Down syndrome. Neurosci Lett. 1997;235(3):137–140
  307. Seidl R, Schuller E, Cairns N, Lubec G. Evidence against increased glycoxidation in patients with Alzheimer's disease. Neurosci Lett. 1997;232(1):49–52
  308. Selley ML, Close DR, Stern SE. The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer's disease. Neurobiol Aging. 2002;23(3):383–388
  309. Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J. 1996;10(7):709–720
  310. Seshadri S, Zornberg GL, Derby LE, Myers MW, Jick H, Drachman DA. Postmenopausal estrogen replacement therapy and the risk of Alzheimer disease. Arch Neurol. 2001;58(3):435–440
  311. Shapiro BL. Whither Down syndrome critical regions?. Hum Genet. 1997;99(3):421–423
  312. Shigenaga MK, Aboujaoude EN, Chen Q, Ames BN. Assays of oxidative DNA damage biomarkers 8-oxo-2′-deoxyguanosine and 8-oxoguanine in nuclear DNA and biological fluids by high-performance liquid chromatography with electrochemical detection. Meth Enzymol. 1994;234:16–33
  313. Shuvaev VV, Laffont I, Serot JM, Fujii J, Taniguchi N, Siest G. Increased protein glycation in cerebrospinal fluid of Alzheimer's disease. Neurobiol Aging. 2001;22(3):397–402
  314. Sikora E, Radziszewska E, Kmiec T, Maslinska D. The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging. Acta Biochim Pol. 1993;40(2):269–272
  315. Sinha S. Antioxidant gene expression imbalance, aging and Down syndrome. Life Sci. 2005;76(12):1407–1426
  316. Siniscalchi A, Mancuso F, Gallelli L, Ferreri IG, Biagio MN, De Sarro G. Increase in plasma homocysteine levels induced by drug treatments in neurologic patients. Pharmacol Res. 2005;52(5):367–375
  317. Smith CD, Carney JM, Starke-Reed PE, Oliver CN, Stadtman ER, Floyd RA, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA. 1991;88(23):10540–10543
  318. Smith CD, Carney JM, Tatsumo T, Stadtman ER, Floyd RA, Markesbery WR. Protein oxidation in aging brain. Ann NY Acad Sci. 1992;663:110–119
  319. Smith MA, Perry G, Richey PL, Sayre LM, Anderson VE, Beal MF, et al. Oxidative damage in Alzheimer's. Nature. 1996;382(6587):120–121
  320. Smith MA, Richey Harris PL, Sayre LM, Beckman JS, Perry G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J Neurosci. 1997;17(8):2653–2657
  321. Smith MA, Sayre LM, Anderson VE, Harris PL, Beal MF, Kowall N, et al. Cytochemical demonstration of oxidative damage in Alzheimer disease by immunochemical enhancement of the carbonyl reaction with 2,4-dinitrophenylhydrazine. J Histochem Cytochem. 1998;46(6):731–735
  322. Smith MA, Sayre LM, Vitek MP, Monnier VM, Perry G. Early AGEing and Alzheimer's. Nature. 1995;374(6520):316
  323. Smith MA, Taneda S, Richey PL, Miyata S, Yan SD, Stern D, et al. Advanced Maillard reaction end-products are associated with Alzheimer disease pathology. Proc Natl Acad Sci USA. 1994;91(12):5710–5714
  324. Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science. 1996;273(5271):59–63
  325. Srinivasan V, Pandi-Perumal SR, Maestroni GJ, Esquifino AI, Hardeland R, Cardinali DP. Role of melatonin in neurodegenerative diseases. Neurotox Res. 2005;7(4):293–318
  326. Stadelmann C, Bruck W, Bancher C, Jellinger K, Lassmann H. Alzheimer disease: DNA fragmentation indicates increased neuronal vulnerability, but not apoptosis. J Neuropathol Exp Neurol. 1998;57(5):56–464
  327. Stadtman ER. Protein oxidation and aging. Science. 1992;257(5074):1220–1224
  328. Steiner ME, Woods WG. Normal formation and repair of gamma-radiation-induced single and double strand DNA breaks in Down syndrome fibroblasts. Mutat Res. 1982;95(2–3):515–523
  329. Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer's disease and duration of NSAID use. Neurology. 1997;48(3):626–632
  330. Stott DJ, MacIntosh G, Lowe GD, Rumley A, McMahon AD, Langhorne P, et al. Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr. 2005;82(6):1320–1326
  331. Su JH, Deng G, Cotman CW. Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer's disease brain. Brain Res. 1997;774(1–2):193–199
  332. Sultana R, Ravagna A, Mohmmad-Abdul H, Calabrese V, Butterfield DA. Ferulic acid ethyl ester protects neurons against amyloid beta- peptide(1–42)-induced oxidative stress and neurotoxicity: relationship to antioxidant activity. J Neurochem. 2005;92(4):749–758
  333. Szekely CA, Thorne JE, Zandi PP, Ek M, Messias E, Breitner JC, et al. Non-steroidal anti-inflammatory drugs for the prevention of Alzheimer's disease: a systematic review. Neuroepidemiology. 2004;23(4):159–169
  334. Tabet N, Birks J, Grimley EJ. Vitamin E for Alzheimer's disease. Cochrane Database Syst Rev. 2000;(4):CD002854
  335. Tabet N, Mantle D, Walker Z, Orrell M. Endogenous antioxidant activities in relation to concurrent Vitamins A, C, and E intake in dementia. Int Psychogeriatr. 2002;14(1):7–15
  336. Tang MX, Jacobs D, Stern Y, Marder K, Schofield P, Gurland B, et al. Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet. 1996;348(9025):429–432
  337. Te Koppele JM, Lucassen PJ, Sakkee AN, Van Asten JG, Ravid R, Swaab DF, et al. 8OHdG levels in brain do not indicate oxidative DNA damage in Alzheimer's disease. Neurobiol Aging. 1996;17(6):819–826
  338. Tedgui A, Mallat Z. Platelets in atherosclerosis: a new role for beta-amyloid peptide beyond Alzheimer's disease. Circ Res. 2002;90(11):1145–1146
  339. Teksen F, Sayli BS, Aydin A, Sayal A, Isimer A. Antioxidative metabolism in Down syndrome. Biol Trace Elem Res. 1998;63(2):123–127
  340. Teunissen CE, de Vente J, Steinbusch HW, De Bruijn C. Biochemical markers related to Alzheimer's dementia in serum and cerebrospinal fluid. Neurobiol Aging. 2002;23(4):485–508
  341. Thiel R, Fowkes SW. Can cognitive deterioration associated with Down syndrome be reduced?. Med Hypotheses. 2005;64(3):524–532
  342. Thomas T. Monoamine oxidase-B inhibitors in the treatment of Alzheimer's disease. Neurobiol Aging. 2000;21(2):343–348
  343. Thomas T, Thomas G, McLendon C, Sutton T, Mullan M. beta-Amyloid-mediated vasoactivity and vascular endothelial damage. Nature. 1996;380(6570):168–171
  344. Thome J, Gsell W, Rosler M, Kornhuber J, Frolich L, Hashimoto E, et al. Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in serum of patients with Alzheimer's disease. Life Sci. 1997;60(1):13–19
  345. Thome J, Munch G, Muller R, Schinzel R, Kornhuber J, Blum-Degen D, et al. Advanced glycation endproducts-associated parameters in the peripheral blood of patients with Alzheimer's disease. Life Sci. 1996;59(8):679–685
  346. Tobi SE, Neary D, Itzhaki RF. Alkylation damage and repair in Alzheimer's disease lymphocytes. Gerontology. 1993;39(5):241–251
  347. Tokuda T, Fukushima T, Ikeda S, Sekijima Y, Shoji S, Yanagisawa N, et al. Plasma levels of amyloid beta proteins Aβ1–40 and Aβ1–42(43) are elevated in Down's syndrome. Ann Neurol. 1997;41(2):271–273
  348. Truelsen T, Thudium D, Gronbaek M. Amount and type of alcohol and risk of dementia: the Copenhagen City Heart Study. Neurology. 2002;59(9):1313–1319
  349. Tuppo EE, Forman LJ. Free radical oxidative damage and Alzheimer's disease. J Am Osteopath Assoc. 2001;101(12 Suppl Pt 1):S11–S15
  350. Tuppo EE, Forman LJ, Spur BW, Chan-Ting RE, Chopra A, Cavalieri TA. Sign of lipid peroxidation as measured in the urine of patients with probable Alzheimer's disease. Brain Res Bull. 2001;54(5):565–568
  351. Urakami K, Kataoka J, Okada A, Isoe K, Wakutani Y, Ji Y, et al. Analysis of amyloid precursor protein mRNAs in skin fibroblasts in Down's syndrome. Dementia. 1996;7(2):82–85
  352. Van Dongen M, van Rossum E, Kessels A, Sielhorst H, Knipschild P. Ginkgo for elderly people with dementia and age-associated memory impairment: a randomized clinical trial. J Clin Epidemiol. 2003;56(4):367–376
  353. van Dongen MC, van Rossum E, Kessels AG, Sielhorst HJ, Knipschild PG. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriatr Soc. 2000;48(10):1183–1194
  354. Varadarajan S, Yatin S, Aksenova M, Butterfield DA. Review: Alzheimer's amyloid β-peptide-associated free radical oxidative stress and neurotoxicity. J Struct Biol. 2000;130(2–3):184–208
  355. Vedder H, Anthes N, Stumm G, Wurz C, Behl C, Krieg JC. Estrogen hormones reduce lipid peroxidation in cells and tissues of the central nervous system. J Neurochem. 1999;72(6):2531–2538
  356. Vina J, Lloret A, Orti R, Alonso D. Molecular bases of the treatment of Alzheimer's disease with antioxidants: prevention of oxidative stress. Mol Aspects Med. 2004;25(1–2):117–123
  357. Vitek MP, Bhattacharya K, Glendening JM, Stopa E, Vlassara H, Bucala R, et al. Advanced glycation end-products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA. 1994;91(11):4766–4770
  358. Wang J, Xiong S, Xie C, Markesbery WR, Lovell MA. Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease. J Neurochem. 2005;93(4):953–962
  359. Wang JZ, Wang ZF. Role of melatonin in Alzheimer-like neurodegeneration. Acta Pharmacol Sin. 2006;27(1):41–49
  360. Wang PN, Liao SQ, Liu RS, Liu CY, Chao HT, Lu SR, et al. Effects of estrogen on cognition, mood, and cerebral blood flow in AD: a controlled study. Neurology. 2000;54(11):2061–2066
  361. Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J. 2004;18(7):790–804
  362. Webber KM, Casadesus G, Marlatt MW, Perry G, Hamlin CR, Atwood CS, et al. Estrogen bows to a new master: the role of gonadotropins in Alzheimer pathogenesis. Ann NY Acad Sci. 2005;1052:201–209
  363. Weinreb O, Mandel S, Amit T, Youdim MB. Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases. J Nutr Biochem. 2004;15(9):506–516
  364. Wettstein A. Cholinesterase inhibitors and Gingko extracts—are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least 6 months’ duration. Phytomedicine. 2000;6(6):393–401
  365. Wisniewski KE, Wisniewski HM, Wen GY. Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Ann Neurol. 1985;17(3):278–282
  366. Wolkowitz OM, Kramer JH, Reus VI, Costa MM, Yaffe K, Walton P, et al. DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study. Neurology. 2003;60(7):1071–1076
  367. Wu FY, Iijima K, Nishida A, Higurashi M. Sister chromatid exchanges in the peripheral lymphocytes of newborns with Down syndrome after in vitro exposure to blue or green light. Mutat Res. 1996;367(4):261–264
  368. Xiang Z, Ho L, Valdellon J, Borchelt D, Kelley K, Spielman L, et al. Cyclooxygenase (COX)-2 and cell cycle activity in a transgenic mouse model of Alzheimer's disease neuropathology. Neurobiol Aging. 2002;23(3):327–334
  369. Yaffe K, Sawaya G, Lieberburg I, Grady D. Estrogen therapy in postmenopausal women: effects on cognitive function and dementia. JAMA. 1998;279(9):688–695
  370. Yan SD, Chen X, Schmidt AM, Brett J, Godman G, Zou YS, et al. Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci USA. 1994;91(16):7787–7791
  371. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, et al. Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280(7):5892–5901
  372. Yankner BA, Duffy LK, Kirschner DA. Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science. 1990;250(4978):279–282
  373. Yatin SM, Varadarajan S, Link CD, Butterfield DA. In vitro and in vivo oxidative stress associated with Alzheimer's amyloid β-peptide (1–42). Neurobiol Aging. 1999;20(3):325–330
  374. Yoo BC, Seidl R, Cairns N, Lubec G. Heat-shock protein 70 levels in brain of patients with Down syndrome and Alzheimer's disease. J Neural Transmemb. 1999;57(Suppl):315–322
  375. Yotti LP, Glover TW, Trosko JE, Segal DJ. Comparative study of X-ray and UV induced cytotoxicity, DNA repair, and mutagenesis in Down's syndrome and normal fibroblasts. Pediatr Res. 1980;14(2):88–92
  376. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature. 2000;407(6805):802–809
  377. Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC. Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology. 2002;59(6):880–886
  378. Zandi PP, Anthony JC, Khachaturian AS, Stone SV, Gustafson D, Tschanz JT, et al. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch Neurol. 2004;61(1):82–88
  379. Zatorska A, Jozwiak Z. Involvement of glutathione and glutathione-related enzymes in the protection of normal and trisomic human fibroblasts against daunorubicin. Cell Biol Int. 2002;26(5):383–391
  380. Zemlan FP, Thienhaus OJ, Bosmann HB. Superoxide dismutase activity in Alzheimer's disease: possible mechanism for paired helical filament formation. Brain Res. 1989;476(1):160–162
  381. Zhao BL, Li XJ, He RG, Cheng SJ, Xin WJ. Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys. 1989;14(2):175–185
  382. Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA, Perry G. Oxidative stress signalling in Alzheimer's disease. Brain Res. 2004;1000(1–2):32–39
  383. Zhu X, Raina AK, Perry G, Smith MA. Alzheimer's disease: the two-hit hypothesis. Lancet Neurol. 2004;3(4):219–226
  384. Zitnanova I, Korytar P, Aruoma OI, Sustrova M, Garaiova I, Muchova J, et al. Uric acid and allantoin levels in Down syndrome: antioxidant and oxidative stress mechanisms?. Clin Chim Acta. 2004;341(1–2):139–146

PII: S0197-4580(06)00093-5

doi: 10.1016/j.neurobiolaging.2006.03.008

Neurobiology of Aging
Volume 28, Issue 5 , Pages 648-676 , May 2007