Epigenetics and Nutrition: B-Vitamin Deprivation and its Impact on Brain Amyloid



Epigenetics is becoming the epicentre of modern medicine because it is beginning to clarify the relationship between genetic background, environment, aging, and disease. SAM-dependent DNA methylation at the 5-position of cytosine within CpG dinucleotides represents an important mechanism for epigenetic control of gene expression and maintenance of genome integrity. Hence, methyl deficiency leads to disturbances in gene expression. B vitamins (B12, B6, and folate) have a pivotal role in reducing homocysteine accumulation by remethylation to form methionine and by transsulfuration to form glutathione (GSH). B vitamins have therefore a central function in SAM synthesis, in gene expression, and in the synthesis of one of the major antioxidant molecules. The physiological causes of AD onset are not yet well understood, but it has been shown that changes in DNA methylation due to vitamin deficiency contributes to the basic mechanisms responsible for AD onset. Accordingly, restoration of gene methylation pattern could be a target for preventing AD or arresting the progression of disease. A methyl donor such as SAM can repair the DNA methylation pattern and thereby restore normal biological functions in AD mice. Recent studies indicate that B vitamin deprivation and SAM supplementation, which modify the SAM cycle, can influence amyloidogenesis in mice, probably via SAM-dependent methylation reactions. SAM supplementation has been shown to reduce beta amyloid in mice brain.


Brain Amyloid Microtubular Network Maximum Potential Lifespan Oncosuppressor Gene Guanine Dinucleotide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Alzheimer Disease




Cytosine-Guanine Dinucleotides
















B6 Vitamin


B12 Vitamin


B9 Vitamin, Tetrahydrofolate


Methylation Potential




Beta Amyloid


Presenilin 1, Gamma-Secretase




Parkinson’s Disease


Asymmetric Dimethylarginine


Nitric Oxide




Nitric Oxide Synthase




Tau Protein


Transgenic Mice Carrying a Human Transgene with a Double Mutation Swedish/Indiana


  1. Bergman Y, Mostoslavsky R. Biol Chem. 1998;379:401–7.PubMedCrossRefGoogle Scholar
  2. Bird A. Nature. 2007;447:396–8.PubMedCrossRefGoogle Scholar
  3. Bottiglieri T. Nutr Rev. 1996;54:382–90.PubMedCrossRefGoogle Scholar
  4. Bottiglieri T, Hyland K. Review Acta Neurol Scand Suppl. 1994;154:19–26.CrossRefGoogle Scholar
  5. Cantoni GL. J Biol Chem. 1951;189:745–54.PubMedGoogle Scholar
  6. Cantoni GL. J Biol Chem. 1953;204:403–16.Google Scholar
  7. Cao X, Sudhof TC. Science. 2001;293:115–20.PubMedCrossRefGoogle Scholar
  8. Cavallaro RA, Fuso A, D’Anselmi F, Seminara L, Scarpa S. J Alzheimers Dis. 2006;9:415–9.PubMedGoogle Scholar
  9. Chiang PK, Gordon RK, Tal J, Zeng GC, Doctor BP, Pardhasaradhi K, McCann PP. FASEB J. 1996;10:471–80.PubMedGoogle Scholar
  10. Cross SH, Meehan RR, Nan X, Bird A. Nat Genet. 1997;16:256–9.PubMedCrossRefGoogle Scholar
  11. De Strooper B. Alzheimer’s disease. Nature. 2000;405:627:9.CrossRefGoogle Scholar
  12. Dolinoy DC. Pharmacogenomics. 2007;8:5–10.PubMedCrossRefGoogle Scholar
  13. Egger G, Liang G, Aparicio A, Jones PA. Nature. 2004;429:457–63.PubMedCrossRefGoogle Scholar
  14. Evans DR, Hemmings BA. Mol Gen Genet. 2000;264:425–32.PubMedCrossRefGoogle Scholar
  15. Fontecave M, Atta M, Mulliez E. Trends Biochem Sci. 2004;29:243–9.PubMedCrossRefGoogle Scholar
  16. Fuso A, Seminara L, Cavallaro RA, D’Anselmi F, Scarpa S. Mol Cell Neurosci. 2005;28:195–204.PubMedCrossRefGoogle Scholar
  17. Fuso A, Cavallaro RA, Zampelli A, D’Anselmi F, Piscopo P, Confaloni A, Scarpa S. J Alzheimers Dis. 2007;11:275–90.PubMedGoogle Scholar
  18. Fuso A, Nicolia V, Cavallaro RA, Ricceri L, D’Anselmi F, Coluccia P, Calamandrei G, Scarpa S. Mol Cell Neurosci. 2008;37:731–46.PubMedCrossRefGoogle Scholar
  19. Fuso A, Nicolia V, Pasqualato A, Fiorenza MT, Cavallaro RA, Scarpa S. Changes in Presenilin 1 gene methylation pattern in diet-induced B vitamin deficiency. Neurobiol Aging. 2010 Epub ahead of print.Google Scholar
  20. Guidi I, Galimberti D, Lonati S, Novembrino C, Bamonti F, Tiriticco M, Fenoglio C, Venturelli E, Baron P, Bresolin N, Scarpini E. Neurobiol Aging. 2006;27:262–9.PubMedCrossRefGoogle Scholar
  21. Hitchler MJ, Domann FE. Free Radic Biol Med. 2007;43:1023–36.PubMedCrossRefGoogle Scholar
  22. Holliday R, Pugh JE. Science. 1975;187:226–32.PubMedCrossRefGoogle Scholar
  23. Joosten E. Clin Chem Lab Med. 2001;39:717–20.PubMedCrossRefGoogle Scholar
  24. Kapoor A, Agius F, Zhu JK. FEBS Lett. 2005;579:5889–98.PubMedCrossRefGoogle Scholar
  25. Kautiainen TL, Jones PA. Biochemistry. 1985;24:5575–81.PubMedCrossRefGoogle Scholar
  26. Kins S, Crameri A, Evans DR, Hemmings BA, Nitsch RM, Gotz J. J Biol Chem. 2001;276:38193–200.PubMedGoogle Scholar
  27. Kresge N, Tabor H, Simoni RD, Hill RL. J Biol Chem. 2005;280:e35.PubMedGoogle Scholar
  28. Kress C, Thomassin H, Grange T. FEBS Lett. 2001;494:135–40.PubMedCrossRefGoogle Scholar
  29. Lee ME, Wang H. Trends Cardiovasc Med. 1999;9:49–54.PubMedCrossRefGoogle Scholar
  30. Levenson JM, Sweatt JD. Cell Mol Life Sci. 2006;63:1009–16.PubMedCrossRefGoogle Scholar
  31. Lichtenthaler SF, Multhaup G, Masters CL, Beyreuther K. FEBS Lett. 1999;453:288–92.PubMedCrossRefGoogle Scholar
  32. Lu SC. Int J Biochem Cell Biol. 2000;32:391–5.PubMedCrossRefGoogle Scholar
  33. Marambaud P, Wen PH, Dutt A, Shioi J, Takashima A, Siman R, Robakis NK. Cell. 2003;114:635–45.PubMedCrossRefGoogle Scholar
  34. Mason JB, Cole BF, Baron JA, Kim YI, Smith AD. Lancet. 2008;371:1335–6.PubMedCrossRefGoogle Scholar
  35. Migliore L, Fontana I, Colognato R, Coppede F, Siciliano G, Murri L. Neurobiol Aging. 2005;26:587–95.PubMedCrossRefGoogle Scholar
  36. Morrison LD, Smith DD, Kish SJ. J Neurochem. 1996;67:1328–31.PubMedCrossRefGoogle Scholar
  37. Nicolia V, Fuso A, Cavallaro RA, Di Luzio A, Scarpa SJ. Alzheimers Dis. 2010;19:895–907.Google Scholar
  38. Okano M, Xie S, Li E. Nat Genet. 1998;19:219–20.PubMedCrossRefGoogle Scholar
  39. Okano M, Bell DW, Haber DA, Li E. Cell. 1999;99:247–57.PubMedCrossRefGoogle Scholar
  40. Quadri P, Fragiacomo C, Pezzati R, Zanda E, Forloni G, Tettamanti M, Lucca U. Am J Clin Nutr. 2004;80:114–22.PubMedGoogle Scholar
  41. Razin A, Riggs AD. DNA methylation and gene function. Science. 1980;210:604–10.PubMedCrossRefGoogle Scholar
  42. Razin A, Szyf M, Kafri T, Roll M, Giloh H, Scarpa S, Carotti D, Cantoni GL. Proc Natl Acad Sci U.S.A. 1986;83:2827–31.PubMedCrossRefGoogle Scholar
  43. Refsum H, Smith AD. Am J Clin Nutr. 2008;88:253–4.PubMedGoogle Scholar
  44. Rouaux C, Jokic N, Mbebi C, Boutillier S, Loeffler JP, Boutillier AL. EMBO J. 2003;22:6537–49.PubMedCrossRefGoogle Scholar
  45. Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao BS, Chattarji S, Kelleher RJ, III, Kandel ER, Duff K, Kirkwood A, Shen J. Neuron. 2004;42:23–36.PubMedCrossRefGoogle Scholar
  46. Scarpa S, Fuso A, D’Anselmi F, Cavallaro RA. FEBS Lett. 2003;541:145–8.PubMedCrossRefGoogle Scholar
  47. Scarpa S, Cavallaro RA, D’Anselmi F, Fuso A. Review J Alzheimers Dis. 2006;9:407–14.Google Scholar
  48. Selhub J, Bagley LC, Miller J, Rosenberg IH. Am J Clin Nutr. 2000;71:614S–20S.PubMedGoogle Scholar
  49. Selley ML. Neurobiol Aging. 2003;24:903–7.PubMedCrossRefGoogle Scholar
  50. Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, Wilson PW, Wolf PA. N Engl J Med. 2002;346:476–83.PubMedCrossRefGoogle Scholar
  51. Siroen MP, Teerlink T, Nijveldt RJ, Prins HA, Richir MC, van Leeuwen PA. Annu Rev Nutr. 2006;26:203–28.PubMedCrossRefGoogle Scholar
  52. Smith AD. Food Nutr Bull. 2008;29:S143–72.PubMedGoogle Scholar
  53. Smith AD, Kim YI, Refsum H. Am J Clin Nutr. 2008;87:517–33.PubMedGoogle Scholar
  54. Sontag E, Hladik C, Montgomery L, Luangpirom A, Mudrak I, Ogris E, White CL, III. J Neuropathol Exp Neurol. 2004;63:1080–91.PubMedGoogle Scholar
  55. Sontag E, Nunbhakdi-Craig V, Sontag JM, Diaz-Arrastia R, Ogris E, Dayal S, Lentz SR, Arning E, Bottiglieri T. J Neurosci. 2007;27:2751–9.PubMedCrossRefGoogle Scholar
  56. Stuhlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Circulation. 2001;104:2569–75.PubMedCrossRefGoogle Scholar
  57. Tabaton M, Tamagno E. Cell Mol Life Sci. 2007;64:2211–8.PubMedCrossRefGoogle Scholar
  58. Takai D, Jones PA. PNAS. 2002;99:3740–5.PubMedCrossRefGoogle Scholar
  59. Troen BR. Mt Sinai J Med. 2003;70:3–22.PubMedGoogle Scholar
  60. Vassar R. Subcell Biochem. 2005;38:79–103.PubMedCrossRefGoogle Scholar
  61. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M. Science. 1999;286:735–41.PubMedCrossRefGoogle Scholar
  62. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di F, V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M. Science. 2001;291:1304–51.PubMedCrossRefGoogle Scholar
  63. Vitvitsky V, Thomas M, Ghorpade A, Gendelman HE, Banerjee R. J Biol Chem. 2006;281:35785–93.PubMedCrossRefGoogle Scholar
  64. Wei H, Ashby DG, Moreno CS, Ogris E, Yeong FM, Corbett AH, Pallas DC. J Biol Chem. 2001;276:1570–7.PubMedCrossRefGoogle Scholar
  65. Weiss A, Cedar H. Genes Cells. 1997;2:481–6.PubMedCrossRefGoogle Scholar
  66. Weiss A, Keshet I, Razin A, Cedar H. Cell. 1996;86:709–18.PubMedCrossRefGoogle Scholar
  67. Xie S, Wang Z, Okano M, Nogami M, Li Y, He WW, Okumura K, Li E. Gene. 1999;236:87–95.PubMedCrossRefGoogle Scholar
  68. Yu XX, Du X, Moreno CS, Green RE, Ogris E, Feng Q, Chou L, McQuoid MJ, Pallas DC. Mol Biol Cell. 2001;12:185–99.PubMedGoogle Scholar
  69. Zafrilla P, Mulero J, Xandri JM, Santo E, Caravaca G, Morillas JM. Curr Med Chem. 2006;13:1075–83.PubMedCrossRefGoogle Scholar
  70. Zhang CE, Tian Q, Wei W, Peng JH, Liu GP, Zhou XW, Wang Q, Wang DW, Wang JZ. Neurobiol Aging. 2008;29:1654–65.PubMedCrossRefGoogle Scholar
  71. Zhao WQ, Feng C, Alkon DL. Neurobiol Dis. 2003;14:458–69.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Dip. di Chirurgia “P. Valdoni”, Centro di Ricerca in Neurobiologia “Daniel Bovet” CriNSapienza Università di RomaRomaItaly

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