Skip to main content
Log in

Aluminium in the human brain

  • Review
  • Published:
Monatshefte für Chemie - Chemical Monthly Aims and scope Submit manuscript

Abstract

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

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Exley C (2009) Trends Biochem Sci 34:589

    Article  CAS  Google Scholar 

  2. Crapper DR, Krisnan SS, Dalton AJ (1973) Science 180:511

    Article  CAS  Google Scholar 

  3. Legendre GR, Alfrey AC (1976) Clin Chem 22:53

    CAS  Google Scholar 

  4. Freundlich M, Zilleruelo G, Abitbol C, Strauss J, Faugere M-C, Malluche HH (1985) Lancet 7:527

    Article  Google Scholar 

  5. Bishop NJ, Robinson MJ, Lendon M, Hewitt CD, Day JP, O’Hara M (1989) Arch Dis Childhood 64:1316

    Article  CAS  Google Scholar 

  6. Bozynski MEA, Sedman AB, Naglie RA, Wright EJ (1989) J Parenteral Enteral Nutr 13:428

    Article  CAS  Google Scholar 

  7. Van Ginkel MF, van der Voet GB, de Wolff FA (1990) Clin Chem 36:658

    Google Scholar 

  8. Yasui M, Yase Y, Ota K, Mukoyama M, Adachi K (1991) NeuroToxicol 12:277

    CAS  Google Scholar 

  9. Lukiw WJ, Krishnan B, Wong L, Kruck PA, Bergeron C, Crapper McLachlan DR (1992) Neurobiol Aging 13:115

    Article  CAS  Google Scholar 

  10. Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Ann Neurol 31:286

    Article  CAS  Google Scholar 

  11. Xu N, Majidi V, Markesbery WR, Ehmann WD (1992) NeuroToxicol 13:735

    CAS  Google Scholar 

  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 107:210

    Article  CAS  Google Scholar 

  13. Lovell MA, Ehmann WD, Markesbery WR (1993) Ann Neurol 33:36

    Article  CAS  Google Scholar 

  14. Moreno A, Dominguez C, Ballbriga A (1994) Acta Paediatr 83:25

    Article  CAS  Google Scholar 

  15. Harrington CR, Wischik CM, McArthur FK, Taylor GA, Edwardson JA, Candy JM (1994) Lancet 343:993

    Article  CAS  Google Scholar 

  16. Bush VJ, Moyer TP, Batts KP, Parisi JE (1995) Clin Chem 41:284

    CAS  Google Scholar 

  17. Hantson P, Mahieu P, Gersdorff M, Sindic C, Lauwerys R (1995) Clin Toxicol 33:645

    Article  CAS  Google Scholar 

  18. Andrási E, Farkas E, Scheibler H, Réffy A, Bezúr L (1995) Arch Gerontol Geriatr 21:89

    Article  Google Scholar 

  19. Galassi G, Cappelli G, Crisi G, Botticelli AR, Lursvarghi E, Winkelmann MD, Lovell MA, Ehmann WD, Markesbery WR (1995) Trace Elem Electrolytes 12:68

    Google Scholar 

  20. Reusche E, Koch V, Friedrich H-J, Nünninghoff D, Stein P, Rob P-M (1996) Clin Neuropathol 15:342

    CAS  Google Scholar 

  21. Deibel MA, Ehmann WD, Candy JM, Ince PG, Shaw PJ, Markesbery WR (1997) Trace Elem Electrolytes 14:51

    CAS  Google Scholar 

  22. Beauchemin D, Kisilevsky R (1998) Anal Chem 70:1026

    Article  CAS  Google Scholar 

  23. Roider G, Drasch G (1999) Trace Elem Electrolytes 16:77

    CAS  Google Scholar 

  24. Reusche E, Pilz P, Oberascher G, Lindner B, Egensperger R, Gloeckner K, Trinka E, Iglseder B (2001) Hum Pathol 32:1136

    Article  CAS  Google Scholar 

  25. Meshitsuka S, Koeda T, Hara T, Takeshita K (2001) Dev Med Child Neurol 43:286

    Article  Google Scholar 

  26. De Wolff FA, Berend K, van der Voet GB (2002) Forensic Sci Int 128:41

    Article  Google Scholar 

  27. Zatta P, Zambenedetti P, Reusche E, Stellmacher F, Cester A, Albanese P, Meneghel G, Nordio M (2004) Nephrol Dial Transplant 19:2929

    Article  Google Scholar 

  28. Andrási E, Páli N, Molnár Z, Kösel S (2005) J Alzheimers Dis 7:273

    Google Scholar 

  29. Exley C, Esiri MM (2006) J Neurol Neurosurg Psychiatry 77:877

    Article  CAS  Google Scholar 

  30. Perl DP, Brody AR (1980) Science 208:297

    Article  CAS  Google Scholar 

  31. Walton JR (2006) Neurotoxicol 27:385

    Article  CAS  Google Scholar 

  32. Yumoto S, Horino Y, Mokuno Y, Kakimi S, Fujii K (1996) Nucl Instr Meth Phys Res B 109/110:362

    Article  CAS  Google Scholar 

  33. Solomon B, Koppel R, Jossiphov J (2001) Brain Res Bull 55:253

    Article  CAS  Google Scholar 

  34. Bouras C, Giannakopoulos P, Good PF, Hsu A, Hof PR, Perl DP (1997) Eur Neurol 38:53

    Article  CAS  Google Scholar 

  35. Hirsch EC, Brandel J-P, Galle P, Javoy-Agid F, Agid Y (1991) J Neurochem 56:446

    Article  CAS  Google Scholar 

  36. Tokutake S, Oyanagi S (1995) Gerontol 52:131

    Article  Google Scholar 

  37. Yumoto S, Kakimi S, Ohsaki A, Ishikawa A (2009) J Inorg Biochem 103:1579

    Article  CAS  Google Scholar 

  38. Bouras C, Giannakopoulos P, Good PF, Hsu A, Hof PR, Perl DP (1996) Acta Neuropathol 92:351

    Article  CAS  Google Scholar 

  39. Aranyosiova M, Kopani M, Rychly B, Jakubovsky J, Velic D (2008) App Surf Sci 255:1123

    Article  CAS  Google Scholar 

  40. Itoh M, Suzuki Y, Sugai K, Ozuka N, Ohsawa M, Otsuki T, Goto Y (2008) J Child Neurol 23:938

    Article  Google Scholar 

  41. Reusche E, Seydel U (1993) Acta Neuropathol 86:249

    Article  CAS  Google Scholar 

  42. Shirabe T, Irie K, Uchida M (2002) Neuropathol 22:206

    Article  Google Scholar 

  43. Exley C, Mamutse G, Korchazhkina O, Pye E, Strekopytov S, Polwart A, Hawkins C (2006) Multiple Sclerosis 12:533

    Article  CAS  Google Scholar 

  44. Exley C, Price NC, Kelly SM, Birchall JD (1993) FEBS Lett 324:293

    Article  CAS  Google Scholar 

  45. Scott CW, Fieles A, Sygowski LA, Caputo CB (1993) Brain Res 628:77

    Article  CAS  Google Scholar 

  46. Uversky VN, Li J, Fink AL (2001) J Biol Chem 276:44284

    Article  CAS  Google Scholar 

  47. Walton JR (2009) Neurotoxicol 30:11059

    Google Scholar 

  48. Exley C, Korchazhkina O, Job D, Strekopytov S, Polwart A, Crome P (2006) J Alzheimers Dis 10:17

    CAS  Google Scholar 

  49. Van Landeghem GF, Dhaese PC, Lamberts LV, Barata JD, DeBroe ME (1997) Nephrol Dial Transplant 12:1692

    Article  Google Scholar 

  50. Eckstein JA, Ammerman GM, Reveles JM, Ackermann BL (2008) J Neurosci Meth 171:190

    Article  CAS  Google Scholar 

  51. Czarnecka J, Cieslak J, Michal K (2005) J Chromatography B 822:85

    Article  CAS  Google Scholar 

  52. Perl DP, Good PF (1987) Lancet 1:1028

    Article  CAS  Google Scholar 

  53. Kumar V, Gill KD (2009) Arch Toxicol 83:965

    Article  CAS  Google Scholar 

  54. Banks WA, Kastin AJ (1983) Lancet 2:1227

    Article  CAS  Google Scholar 

  55. Beardmore J, Exley C (2009) J Inorg Biochem 103:205

    Article  CAS  Google Scholar 

  56. Exley C (2004) Free Rad Biol Med 36:380

    Article  CAS  Google Scholar 

  57. Khan A, Dobson J, Exley C (2006) Free Rad Biol Med 40:557

    Article  CAS  Google Scholar 

  58. Exley C (1999) J Inorg Biochem 76:133

    Article  CAS  Google Scholar 

  59. Abbracchio MP, Burnstock G, Verkhratsky A, Zimmerman H (2009) Trends Neurosci 32:19

    Article  CAS  Google Scholar 

  60. Lukiw WJ (2010) J Inorg Biochem 104:1010

    Article  CAS  Google Scholar 

  61. Karlik SJ, Eichhorn GL, McLachlan DRC (1980) Neurotoxicol 1:83

    CAS  Google Scholar 

  62. Chen L, Yokel RA, Hennig B, Toborek M (2008) J Neuroimmune Pharmacol 3:286

    Article  Google Scholar 

  63. Exley C, Siesjö P, Eriksson H (2010) Trends Immunol 31:103

    Article  CAS  Google Scholar 

  64. Becaria A, Lahiri DK, Bondy SC, Chen DM, Hamadeh A, Li H, Taylor R, Campbell A (2006) J Neuroimmunol 176:16

    Article  CAS  Google Scholar 

  65. Perl DP, Fogarty U, Harpaz N, Sachar DB (2004) Inflamm Bowel Dis 10:881

    Article  Google Scholar 

  66. Campbell A, Bondy SC (2000) Cell Mol Biol 46:721

    CAS  Google Scholar 

  67. Exley C (2003) J Inorg Biochem 97:1

    Article  CAS  Google Scholar 

  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 45

    Google Scholar 

  69. Exley C, House E, Collingwood JF, Davidson M, Cannon D, Donald AM (2010) J Alzheimers Dis 20:1159

    CAS  Google Scholar 

Download references

Acknowledgments

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher Exley.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Exley, C., House, E.R. Aluminium in the human brain. Monatsh Chem 142, 357–363 (2011). https://doi.org/10.1007/s00706-010-0417-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00706-010-0417-y

Keywords

Navigation