Monatshefte für Chemie - Chemical Monthly

, Volume 142, Issue 4, pp 357–363 | Cite as

Aluminium in the human brain

  • Christopher ExleyEmail author
  • Emily R. House


An inevitable consequence of humans living in the Aluminium Age is the presence of aluminium in the brain. This non-essential, neurotoxic metal gains entry to the brain throughout all stages of human development, from the foetus through to old age. Human exposure to myriad forms of this ubiquitous and omnipresent metal makes its presence in the brain inevitable, while the structure and physiology of the brain makes it particularly susceptible to the accumulation of aluminium with age. In spite of aluminium’s complete lack of biological essentiality, it actually participates avidly in brain biochemistry and substitutes for essential metals in critical biochemical processes. The degree to which such substitutions are disruptive and are manifested as biological effects will depend upon the biological availability of aluminium in any particular physical or chemical compartment, and will under all circumstances be exerting an energy load on the brain. In short, the brain must expend energy in its ‘unconscious’ response to an exposure to biologically available aluminium. There are many examples where ‘biological effect’ has resulted in aluminium-induced neurotoxicity and most potently in conditions that have resulted in an aluminium-associated encephalopathy. However, since aluminium is non-essential and not required by the brain, its biological availability will only rarely achieve such levels of acuity, and it is more pertinent to consider and investigate the brain’s response to much lower though sustained levels of biologically reactive aluminium. This is the level of exposure that defines the putative role of aluminium in chronic neurodegenerative disease and, though thoroughly investigated in numerous animal models, the chronic toxicity of aluminium has yet to be addressed experimentally in humans. A feasible test of the ‘aluminium hypothesis’, whereby aluminium in the human brain is implicated in chronic neurodegenerative disease, would be to reduce the brain’s aluminium load to the lowest possible level by non-invasive means. The simplest way that this aim can be fulfilled in a significant and relevant population is by facilitating the urinary excretion of aluminium through the regular drinking of a silicic acid-rich mineral water over an extended time period. This will lower the body and brain burden of aluminium, and by doing so will test whether brain aluminium contributes significantly to chronic neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

Graphical Abstract

The co-localisation of aluminium (purple) and amyloid (red) in human brain tissue


Metal Neurodegenerative disease Neuropathology Neurotoxicity Alzheimer’s disease Parkinson’s disease 



Andrew Lawrence (Keele, KUDIS) is thanked for help in preparing Fig. 2. G Forster and Professor PG Ince (Royal Hallamshire Hospital, Sheffield) are thanked for help in providing brain tissues from MRC CFAS.


  1. 1.
    Exley C (2009) Trends Biochem Sci 34:589CrossRefGoogle Scholar
  2. 2.
    Crapper DR, Krisnan SS, Dalton AJ (1973) Science 180:511CrossRefGoogle Scholar
  3. 3.
    Legendre GR, Alfrey AC (1976) Clin Chem 22:53Google Scholar
  4. 4.
    Freundlich M, Zilleruelo G, Abitbol C, Strauss J, Faugere M-C, Malluche HH (1985) Lancet 7:527CrossRefGoogle Scholar
  5. 5.
    Bishop NJ, Robinson MJ, Lendon M, Hewitt CD, Day JP, O’Hara M (1989) Arch Dis Childhood 64:1316CrossRefGoogle Scholar
  6. 6.
    Bozynski MEA, Sedman AB, Naglie RA, Wright EJ (1989) J Parenteral Enteral Nutr 13:428CrossRefGoogle Scholar
  7. 7.
    Van Ginkel MF, van der Voet GB, de Wolff FA (1990) Clin Chem 36:658Google Scholar
  8. 8.
    Yasui M, Yase Y, Ota K, Mukoyama M, Adachi K (1991) NeuroToxicol 12:277Google Scholar
  9. 9.
    Lukiw WJ, Krishnan B, Wong L, Kruck PA, Bergeron C, Crapper McLachlan DR (1992) Neurobiol Aging 13:115CrossRefGoogle Scholar
  10. 10.
    Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Ann Neurol 31:286CrossRefGoogle Scholar
  11. 11.
    Xu N, Majidi V, Markesbery WR, Ehmann WD (1992) NeuroToxicol 13:735Google Scholar
  12. 12.
    Candy JM, McArthur FK, Oakley AE, Taylor GA, Chen CPL-H, Mountfort SA, Thompson JE, Chalker PR, Bishop HE, Beyreuther K, Perry G, Ward MK, Martyn CN, Edwardson JA (1992) J Neurolog Sci 107:210CrossRefGoogle Scholar
  13. 13.
    Lovell MA, Ehmann WD, Markesbery WR (1993) Ann Neurol 33:36CrossRefGoogle Scholar
  14. 14.
    Moreno A, Dominguez C, Ballbriga A (1994) Acta Paediatr 83:25CrossRefGoogle Scholar
  15. 15.
    Harrington CR, Wischik CM, McArthur FK, Taylor GA, Edwardson JA, Candy JM (1994) Lancet 343:993CrossRefGoogle Scholar
  16. 16.
    Bush VJ, Moyer TP, Batts KP, Parisi JE (1995) Clin Chem 41:284Google Scholar
  17. 17.
    Hantson P, Mahieu P, Gersdorff M, Sindic C, Lauwerys R (1995) Clin Toxicol 33:645CrossRefGoogle Scholar
  18. 18.
    Andrási E, Farkas E, Scheibler H, Réffy A, Bezúr L (1995) Arch Gerontol Geriatr 21:89CrossRefGoogle Scholar
  19. 19.
    Galassi G, Cappelli G, Crisi G, Botticelli AR, Lursvarghi E, Winkelmann MD, Lovell MA, Ehmann WD, Markesbery WR (1995) Trace Elem Electrolytes 12:68Google Scholar
  20. 20.
    Reusche E, Koch V, Friedrich H-J, Nünninghoff D, Stein P, Rob P-M (1996) Clin Neuropathol 15:342Google Scholar
  21. 21.
    Deibel MA, Ehmann WD, Candy JM, Ince PG, Shaw PJ, Markesbery WR (1997) Trace Elem Electrolytes 14:51Google Scholar
  22. 22.
    Beauchemin D, Kisilevsky R (1998) Anal Chem 70:1026CrossRefGoogle Scholar
  23. 23.
    Roider G, Drasch G (1999) Trace Elem Electrolytes 16:77Google Scholar
  24. 24.
    Reusche E, Pilz P, Oberascher G, Lindner B, Egensperger R, Gloeckner K, Trinka E, Iglseder B (2001) Hum Pathol 32:1136CrossRefGoogle Scholar
  25. 25.
    Meshitsuka S, Koeda T, Hara T, Takeshita K (2001) Dev Med Child Neurol 43:286CrossRefGoogle Scholar
  26. 26.
    De Wolff FA, Berend K, van der Voet GB (2002) Forensic Sci Int 128:41CrossRefGoogle Scholar
  27. 27.
    Zatta P, Zambenedetti P, Reusche E, Stellmacher F, Cester A, Albanese P, Meneghel G, Nordio M (2004) Nephrol Dial Transplant 19:2929CrossRefGoogle Scholar
  28. 28.
    Andrási E, Páli N, Molnár Z, Kösel S (2005) J Alzheimers Dis 7:273Google Scholar
  29. 29.
    Exley C, Esiri MM (2006) J Neurol Neurosurg Psychiatry 77:877CrossRefGoogle Scholar
  30. 30.
    Perl DP, Brody AR (1980) Science 208:297CrossRefGoogle Scholar
  31. 31.
    Walton JR (2006) Neurotoxicol 27:385CrossRefGoogle Scholar
  32. 32.
    Yumoto S, Horino Y, Mokuno Y, Kakimi S, Fujii K (1996) Nucl Instr Meth Phys Res B 109/110:362CrossRefGoogle Scholar
  33. 33.
    Solomon B, Koppel R, Jossiphov J (2001) Brain Res Bull 55:253CrossRefGoogle Scholar
  34. 34.
    Bouras C, Giannakopoulos P, Good PF, Hsu A, Hof PR, Perl DP (1997) Eur Neurol 38:53CrossRefGoogle Scholar
  35. 35.
    Hirsch EC, Brandel J-P, Galle P, Javoy-Agid F, Agid Y (1991) J Neurochem 56:446CrossRefGoogle Scholar
  36. 36.
    Tokutake S, Oyanagi S (1995) Gerontol 52:131CrossRefGoogle Scholar
  37. 37.
    Yumoto S, Kakimi S, Ohsaki A, Ishikawa A (2009) J Inorg Biochem 103:1579CrossRefGoogle Scholar
  38. 38.
    Bouras C, Giannakopoulos P, Good PF, Hsu A, Hof PR, Perl DP (1996) Acta Neuropathol 92:351CrossRefGoogle Scholar
  39. 39.
    Aranyosiova M, Kopani M, Rychly B, Jakubovsky J, Velic D (2008) App Surf Sci 255:1123CrossRefGoogle Scholar
  40. 40.
    Itoh M, Suzuki Y, Sugai K, Ozuka N, Ohsawa M, Otsuki T, Goto Y (2008) J Child Neurol 23:938CrossRefGoogle Scholar
  41. 41.
    Reusche E, Seydel U (1993) Acta Neuropathol 86:249CrossRefGoogle Scholar
  42. 42.
    Shirabe T, Irie K, Uchida M (2002) Neuropathol 22:206CrossRefGoogle Scholar
  43. 43.
    Exley C, Mamutse G, Korchazhkina O, Pye E, Strekopytov S, Polwart A, Hawkins C (2006) Multiple Sclerosis 12:533CrossRefGoogle Scholar
  44. 44.
    Exley C, Price NC, Kelly SM, Birchall JD (1993) FEBS Lett 324:293CrossRefGoogle Scholar
  45. 45.
    Scott CW, Fieles A, Sygowski LA, Caputo CB (1993) Brain Res 628:77CrossRefGoogle Scholar
  46. 46.
    Uversky VN, Li J, Fink AL (2001) J Biol Chem 276:44284CrossRefGoogle Scholar
  47. 47.
    Walton JR (2009) Neurotoxicol 30:11059Google Scholar
  48. 48.
    Exley C, Korchazhkina O, Job D, Strekopytov S, Polwart A, Crome P (2006) J Alzheimers Dis 10:17Google Scholar
  49. 49.
    Van Landeghem GF, Dhaese PC, Lamberts LV, Barata JD, DeBroe ME (1997) Nephrol Dial Transplant 12:1692CrossRefGoogle Scholar
  50. 50.
    Eckstein JA, Ammerman GM, Reveles JM, Ackermann BL (2008) J Neurosci Meth 171:190CrossRefGoogle Scholar
  51. 51.
    Czarnecka J, Cieslak J, Michal K (2005) J Chromatography B 822:85CrossRefGoogle Scholar
  52. 52.
    Perl DP, Good PF (1987) Lancet 1:1028CrossRefGoogle Scholar
  53. 53.
    Kumar V, Gill KD (2009) Arch Toxicol 83:965CrossRefGoogle Scholar
  54. 54.
    Banks WA, Kastin AJ (1983) Lancet 2:1227CrossRefGoogle Scholar
  55. 55.
    Beardmore J, Exley C (2009) J Inorg Biochem 103:205CrossRefGoogle Scholar
  56. 56.
    Exley C (2004) Free Rad Biol Med 36:380CrossRefGoogle Scholar
  57. 57.
    Khan A, Dobson J, Exley C (2006) Free Rad Biol Med 40:557CrossRefGoogle Scholar
  58. 58.
    Exley C (1999) J Inorg Biochem 76:133CrossRefGoogle Scholar
  59. 59.
    Abbracchio MP, Burnstock G, Verkhratsky A, Zimmerman H (2009) Trends Neurosci 32:19CrossRefGoogle Scholar
  60. 60.
    Lukiw WJ (2010) J Inorg Biochem 104:1010CrossRefGoogle Scholar
  61. 61.
    Karlik SJ, Eichhorn GL, McLachlan DRC (1980) Neurotoxicol 1:83Google Scholar
  62. 62.
    Chen L, Yokel RA, Hennig B, Toborek M (2008) J Neuroimmune Pharmacol 3:286CrossRefGoogle Scholar
  63. 63.
    Exley C, Siesjö P, Eriksson H (2010) Trends Immunol 31:103CrossRefGoogle Scholar
  64. 64.
    Becaria A, Lahiri DK, Bondy SC, Chen DM, Hamadeh A, Li H, Taylor R, Campbell A (2006) J Neuroimmunol 176:16CrossRefGoogle Scholar
  65. 65.
    Perl DP, Fogarty U, Harpaz N, Sachar DB (2004) Inflamm Bowel Dis 10:881CrossRefGoogle Scholar
  66. 66.
    Campbell A, Bondy SC (2000) Cell Mol Biol 46:721Google Scholar
  67. 67.
    Exley C (2003) J Inorg Biochem 97:1CrossRefGoogle Scholar
  68. 68.
    Exley C (2009) Aluminium and medicine. In: Merce ALR, Felcman J, Recio MAL (eds) Molecular and supramolecular bioinorganic chemistry: applications in medical sciences. Nova Science Pub Inc, New York, p 45Google Scholar
  69. 69.
    Exley C, House E, Collingwood JF, Davidson M, Cannon D, Donald AM (2010) J Alzheimers Dis 20:1159Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.The Birchall Centre, Lennard-Jones LaboratoriesKeele UniversityStaffordshireUK

Personalised recommendations