Journal of Neurology

, Volume 255, Issue 11, pp 1652–1656 | Cite as

Increased serum ferritin levels in amyotrophic lateral sclerosis (ALS) patients

Original Communication

Abstract

Iron misregulation promotes oxidative stress, a proposed pathological mechanism in neurodegenerative disease. The aim of this study was to evaluate serum iron metabolism indicators in 60 amyotrophic lateral sclerosis (ALS) patients and 44 age matched controls. Serum ferritin levels were significantly increased in ALS patients compared to controls (p < 0.001), while no differences in the levels of serum iron, transferrin, iron saturation or total iron binding capacity were found. Likewise no differences in C reactive protein (CRP) or caeruloplasmin were detected, suggesting that the elevated ferritin levels in ALS did not merely indicate an acute phase response. The increased ferritin level may reflect a general increase in stored iron or be a consequence of ongoing muscle degeneration.

Key words

amyotrophic lateral sclerosis iron metabolism serum ferritin 

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References

  1. 1.
    Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, Dawkins FW, Acton RT, Harris EL, Gordeuk VR, Leiendecker-Foster C, Speechley M, Snively BM, Holup JL, Thomson E, Sholinsky P (2005) Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 352:1769–1778PubMedCrossRefGoogle Scholar
  2. 2.
    Bonnefont-Rousselot D, Lacomblez L, Jaudon MC, Lepage S, Salachas F, Bensimon G, Bizard C, Doppler V, Delattre J, Meininger V (2000) Blood oxidative stress in amyotrophic lateral sclerosis. J Neurol Sci 178:57–62PubMedCrossRefGoogle Scholar
  3. 3.
    Boulton FE (1973) The myoglobin content of human skeletal muscle. Br J Haematol 25:281PubMedGoogle Scholar
  4. 4.
    Cook JD, Lipschitz DA, Miles LE, Finch CA (1974) Serum ferritin as a measure of iron stores in normal subjects. Am J Clin Nutr 27:681–687PubMedGoogle Scholar
  5. 5.
    Danzeisen R, Achsel T, Bederke U, Cozzolino M, Crosio C, Ferri A, Frenzel M, Gralla EB, Huber L, Ludolph A, Nencini M, Rotilio G, Valentine JS, Carri MT (2006) Superoxide dismutase 1 modulates expression of transferrin receptor. J Biol Inorg Chem 11:489–498PubMedCrossRefGoogle Scholar
  6. 6.
    Doherty CP (2007) Host-pathogen interactions: the role of iron. J Nutr 137:1341–1344PubMedGoogle Scholar
  7. 7.
    Goldknopf IL, Sheta EA, Bryson J, Folsom B, Wilson C, Duty J, Yen AA, Appel SH (2006) Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson’s disease. Biochem Biophys Res Commun 342:1034–1039PubMedCrossRefGoogle Scholar
  8. 8.
    Goodall EF, Greenway MJ, van Marion I, Carroll CB, Hardiman O, Morrison KE (2005) Association of the H63D polymorphism in the hemochromatosis gene with sporadic ALS. Neurology 65:934–937PubMedCrossRefGoogle Scholar
  9. 9.
    Ince PG, Shaw PJ, Candy JM, Mantle D, Tandon L, Ehmann WD, Markesbery WR (1994) Iron, selenium and glutathione peroxidase activity are elevated in sporadic motor neuron disease. Neurosci Lett 182:87–90PubMedCrossRefGoogle Scholar
  10. 10.
    Kasarskis EJ, Tandon L, Lovell MA, Ehmann WD (1995) Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study. J Neurol Sci 130:203–208PubMedCrossRefGoogle Scholar
  11. 11.
    Kitahara T, Kiryu S, Takeda N, Kubo T, Kiyama H (1995) Up-regulation of ferritin heavy chain mRNA expression in the rat skeletal muscle after denervation: detected by means of differential display. Neurosci Res 23:353–360PubMedCrossRefGoogle Scholar
  12. 12.
    Markesbery WR, Ehmann WD, Candy JM, Ince PG, Shaw PJ, Tandon L, Deibel MA (1995) Neutron activation analysis of trace elements in motor neuron disease spinal cord. Neurodegeneration 4:383–390PubMedCrossRefGoogle Scholar
  13. 13.
    Milne DB, Johnson PE (1993) Assessment of copper status: effect of age and gender on reference ranges in healthy adults. Clin Chem 39:883–887PubMedGoogle Scholar
  14. 14.
    Mizuno Y, Amari M, Takatama M, Aizawa H, Mihara B, Okamoto K (2006) Transferrin localizes in Bunina bodies in amyotrophic lateral sclerosis. Acta Neuropathol (Berl) 112:597–603PubMedCrossRefGoogle Scholar
  15. 15.
    Moreau C, Devos D, Brunaud-Danel V, Defebvre L, Perez T, Destee A, Tonnel AB, Lassalle P, Just N (2005) Elevated IL-6 and TNF-alpha levels in patients with ALS: inflammation or hypoxia? Neurology 65:1958–1960PubMedCrossRefGoogle Scholar
  16. 16.
    Muller FL, Song W, Jang Y, Liu Y, Sabia M, Richardson A, Van Remmen H (2007) Denervation-Induced Skeletal Muscle Atrophy is Associated with Increased Mitochondrial ROS Production. Am J Physiol Regul Integr Comp Physiol 293:R1159–R1168PubMedGoogle Scholar
  17. 17.
    Poloni M, Facchetti D, Mai R, Micheli A, Agnoletti L, Francolini G, Mora G, Camana C, Mazzini L, Bachetti T (2000) Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis. Neurosci Lett 287:211–214PubMedCrossRefGoogle Scholar
  18. 18.
    Restagno G, Lombardo F, Ghiglione P, Calvo A, Cocco E, Sbaiz L, Mutani R, Chio A (2007) HFE H63D polymorphism is increased in patients with amyotrophic lateral sclerosis of Italian origin. J Neurol Neurosurg Psychiatry 78:327PubMedCrossRefGoogle Scholar
  19. 19.
    Simpson EP, Henry YK, Henkel JS, Smith RG, Appel SH (2004) Increased lipid peroxidation in sera of ALS patients – A potential biomarker of disease burden. Neurology 62:1758–1765PubMedGoogle Scholar
  20. 20.
    Sutedja NA, Sinke RJ, Van Vught PW, Van der Linden MW, Wokke JH, van Duijn CM, Njajou OT, Van der Schouw YT, Veldink JH, van den Berg LH (2007) The association between H63D mutations in HFE and amyotrophic lateral sclerosis in a Dutch population. Arch Neurol 64:63–67PubMedCrossRefGoogle Scholar
  21. 21.
    Thompson KJ, Shoham S, Connor JR (2001) Iron and neurodegenerative disorders. Brain Res Bull 55:155–164PubMedCrossRefGoogle Scholar
  22. 22.
    Torti FM, Torti SV (2002) Regulation of ferritin genes and protein. Blood 99:3505–3516PubMedCrossRefGoogle Scholar
  23. 23.
    Wang XS, Lee S, Simmons Z, Boyer P, Scott K, Liu W, Connor J (2004) Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences. J Neurol Sci 227:27–33PubMedCrossRefGoogle Scholar
  24. 24.
    Yasui M, Ota K, Garruto RM (1993) Concentrations of zinc and iron in the brains of Guamanian patients with amyotrophic lateral sclerosis and parkinsonism- dementia. Neurotoxicology 14:445–450PubMedGoogle Scholar
  25. 25.
    Zappone E, Bellotti V, Cazzola M, Ceroni M, Meloni F, Pedrazzoli P, Perfetti V (1986) Cerebrospinal fluid ferritin in human disease. Haematologica 71:103–107PubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • E. F. Goodall
    • 1
  • M. S. Haque
    • 2
  • K. E. Morrison
    • 1
    • 3
  1. 1.Molecular Neurology Group, Division of NeuroscienceInstitute of Biomedical Research, The Medical School, University of BirminghamEdgbaston, BirminghamUK
  2. 2.Dept. of Primary Care and General PracticeUniversity of BirminghamBirminghamUK
  3. 3.Dept. of Neurology, Queen Elizabeth HospitalUniversity Hospitals Birmingham NHS, Foundation TrustBirminghamUK

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