Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men

Journal of Alzheimer's Disease

Volumn 20, Issue 1, 2010, Pages 333-341

  Bartzokis, George ^a,b,c   Lu, Po H ^b   Tishler, Todd A ^a,c   Peters, Douglas G ^a,c   Kosenko, Anastasia ^a,c   Barrall, Katherine A ^a   Finn, J Paul ^b   Villablanca, Pablo ^b   Laub, Gerhard ^d   Altshuler, Lori L ^a,c   Geschwind, Daniel H ^b   Mintz, Jim ^e   Neely, Elizabeth ^f   Connor, James R ^f  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c VA GREATER LOS ANGELES HEALTHCARE SYSTEM   (United States)

^d SIEMENS CORPORATE RESEARCH   (United States)

^e UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^f PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

Author keywords

Alpha synuclein; amyloid; basal ganglia; chelation; dementia; diet; free radicals; gene; gray matter; iron; Lewy body; metal; myelin; oligodendrocytes; prevention; risk; tau; treatment

Indexed keywords

APOLIPOPROTEIN E4; FERRITIN; HFE PROTEIN; IRON; TRANSFERRIN; TRANSFERRIN C2; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CAUDATE NUCLEUS; CONTROLLED STUDY; CORPUS CALLOSUM; FEMALE; FERRITIN BLOOD LEVEL; FRONTAL LOBE; GENETIC VARIABILITY; GENOTYPE; GLOBUS PALLIDUS; HIPPOCAMPUS; HUMAN; HUMAN EXPERIMENT; IRON BLOOD LEVEL; IRON METABOLISM; MALE; NORMAL HUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; PUTAMEN; THALAMUS; WHITE MATTER;

EID: 77953119097     PISSN: 13872877     EISSN: None     Source Type: Journal    
DOI: 10.3233/JAD-2010-1368     Document Type: Article

References (67)

1. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR (2004) Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 5, 863-873.
2. Youdim MB (2008) Brain iron deficiency and excess; cognitive impairment and neurodegeneration with involvement of striatum and hippocampus. Neurotox Res 14, 45-56.
3. Bartzokis G (2009) Alzheimer's disease as homeostatic responses to age-related myelin breakdown. Neurobiol Aging, in press.
4. Kell DB (2009) Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics 2, 2.
5. Altamura S, Muckenthaler MU (2009) Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. J Alzheimers Dis 16, 879-895.
6. Meadowcroft MD, Connor JR, Smith MB, Yang QX (2009) MRI and histological analysis of beta-amyloid plaques in both human Alzheimer's disease and APP/PS1 transgenic mice. J Magn Reson Imaging 29, 997-1007.
7. Bartzokis G, Lu PH, Mintz J (2007) Human brain myelination and amyloid beta deposition in Alzheimer's disease. Alzheimers Dement 3, 122-125.
8. Bush AI, Tanzi RE (2008) Therapeutics for Alzheimer's disease based on the metal hypothesis. Neurotherapeutics 5, 421-432.
9. Smith MA, Zhu X, Tabaton M, Liu G, McKeel Jr DW, Cohen ML, Wang X, Siedlak SL, Dwyer BE, Hayashi T, Nakamura M, Nunomura A, Perry G (2010) Increased iron and free radical generation in preclinical alzheimer disease and mild cognitive impairment. J Alzheimers Dis 19, 363-372.
10. Hallgren B, Sourander P (1958) The effect of age on the nonhaemin iron in the human brain. J Neurochem 3, 41-51.
11. Klintworth GK (1973) Huntington's chorea - morphologic contributions of a century In Advances in Neurology, v.1: Huntington's chorea, 1872-1972, Barbeau A, Paulson GW, Chase TN, eds. Raven Press, New York, pp. 353-368.
12. Hirose W, Ikematsu K, Tsuda R (2003) Age-associated increases in heme oxygenase-1 and ferritin immunoreactivity in the autopsied brain. Leg Med (Tokyo) 5(Suppl 1), S360-366.
13. Bartzokis G, Mintz J, Sultzer D, Marx P, Herzberg JS, Phelan CK, Marder SR (1994) In vivo MR evaluation of age-related increases in brain iron. AJNR Am J Neuroradiol 15, 1129-1138.
14. Bartzokis G, Beckson M, Hance DB, Marx P, Foster JA, Marder SR (1997) MR evaluation of age-related increase of brain iron in young adult and older normal males. Magn Reson Imaging 15, 29-35.
15. Bartzokis G, Tishler TA, Lu PH, Villablanca P, Altshuler LL, Carter M, Huang D, Edwards N, Mintz J (2007) Brain ferritin iron may influence age- and gender-related risks of neurodegeneration. Neurobiol Aging 28, 414-423.
16. Bartzokis G, Tishler TA, Shin I-S, Lu PH, Cummings JL (2004) Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases. In Redox-active Metals in Neurological Disorders, LeVine S, Connor J, Schipper H, eds. Ann N Y Acad Sci, New York, pp. 224-236.
17. Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, Nelson LM (2003) Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol 157, 1015-1022.
18. Haaxma CA, Bloem BR, Borm GF, Oyen WJ, Leenders KL, Eshuis S, Booij J, Dluzen DE, Horstink MW (2006) Gender differences in Parkinson's disease. J Neurol Neurosurg Psychiatry 78, 819-824
19. Bartzokis G, Cummings JL, Markham CH, Marmarelis PZ, Treciokas LJ, Tishler TA, Marder SR, Mintz J (1999) MRI evaluation of brain iron in earlier- and later-onset Parkinson's disease and normal subjects. Magn Reson Imaging 17, 213-222.
20. Barker WW, Luis CA, Kashuba A, Luis M, Harwood DG, Loewenstein D, Waters C, Jimison P, Shepherd E, Sevush S, Graff-Radford N, Newland D, Todd M, Miller B, Gold M, Heilman K, Doty L, Goodman I, Robinson B, Pearl G, Dickson D, Duara R (2002) Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the state of Florida brain bank. Alzheimer Dis Assoc Disord 16, 203-212.
21. Miech RA, Breitner JC, Zandi PP, Khachaturian AS, Anthony JC, Mayer L (2002) Incidence of AD may decline in the early 90s for men, later for women: The Cache County study. Neurology 58, 209-218.
22. Raber J, Huang Y, Ashford JW (2004) ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol Aging 25, 641-650.
23. Alizadeh BZ, Njajou OT, Millan MR, Hofman A, Breteler MM, van Duijn CM (2009) HFE variants, APOE and Alzheimer's disease: Findings from the population-based Rotterdam Study. Neurobiol Aging 30, 330-332.
24. Moalem S, Percy ME, Andrews DF, Kruck TP, Wong S, Dalton AJ, Mehta P, Fedor B, Warren AC (2000) Are hereditary hemochromatosis mutations involved in Alzheimer disease? Am J Med Genet 93, 58-66.
25. Sampietro M, Caputo L, Casatta A, Meregalli M, Pellagatti A, Tagliabue J, Annoni G, Vergani C (2001) The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease. Neurobiol Aging 22, 563-568.
26. Combarros O, Garcia-Roman M, Fontalba A, Fernandez- Luna JL, Llorca J, Infante J, Berciano J (2003) Interaction of the H63D mutation in the hemochromatosis gene with the apolipoprotein E epsilon 4 allele modulates age at onset of Alzheimer's disease. Dement Geriatr Cogn Disord 15, 151-154.
27. Lehmann DJ, Worwood M, Ellis R, Wimhurst VL, Merryweather-Clarke AT,Warden DR, Smith AD, Robson KJ (2006) Iron genes, iron load and risk of Alzheimer's disease. J Med Genet 43, e52.
28. Connor JR, Lee SY (2006) HFE mutations and Alzheimer's disease. J Alzheimers Dis 10, 267-276.
29. Rondeau V, Iron A, Letenneur L, Commenges D, Duchene F, Arveiler B, Dartigues JF (2006) Analysis of the effect of aluminum in drinking water and transferrin C2 allele on Alzheimer's disease. Eur J Neurol 13, 1022-1025.
30. Burt MJ, George PM, Upton JD, Collett JA, Frampton CM, Chapman TM, Walmsley TA, Chapman BA (1998) The significance of haemochromatosis gene mutations in the general population: implications for screening. Gut 43, 830-836.
31. Pulliam JF, Jennings CD, Kryscio RJ, Davis DG, Wilson D, Montine TJ, Schmitt FA, Markesbery WR (2003) Association of HFE mutations with neurodegeneration and oxidative stress in Alzheimer's disease and correlation with APOE. Am J Med Genet 119B, 48-53.
32. 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, 27-33.
33. Mitchell RM, Freeman WM, Randazzo WT, Stephens HE, Beard JL, Simmons Z, Connor JR (2009) A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis. Neurology 72, 14-19.
34. Demarquay G, Setiey A, Morel Y, Trepo C, Chazot G, Broussolle E (2000) Clinical report of three patients with hereditary hemochromatosis and movement disorders. Mov Disord 15, 1204-1209.
35. Dekker MC, Giesbergen PC, Njajou OT, van Swieten JC, Hofman A, Breteler MM, van Duijn CM (2003) Mutations in the hemochromatosis gene (HFE), Parkinson's disease and parkinsonism. Neurosci Lett 348, 117-119.
36. Todorich B, Pasquini JM, Garcia CI, Paez PM, Connor JR (2009) Oligodendrocytes and myelination: The role of iron. Glia 57, 467-478.
37. Bartzokis G, Aravagiri M, Oldendorf WH, Mintz J, Marder SR (1993) Field dependent transverse relaxation rate increase may be a specific measure of tissue iron stores. Magn Reson Med 29, 459-464.
38. Vymazal J, Brooks RA, Baumgarner C, Tran V, Katz D, Bulte JW, Bauminger R, Di Chiro G (1996) The relation between brain iron and NMR relaxation times: An in vitro study. Magn Reson Med 35, 56-61.
39. Floyd RA, Carney JM (1993) The role of metal ions in oxidative processes and aging. Toxicol Ind Health 9, 197-214.
40. Morris CM, Candy JM, Oakley AE, Bloxham CA, Edwardson JA (1992) Histochemical distribution of non-haem iron in the human brain. Acta Anat (Basel) 144, 235-257.
41. Bartzokis G, Sultzer D, Cummings BJ, Holt LE, Hance DB, HendersonVW, Mintz J (2000) In vivo evaluation of brain iron in Alzheimer's disease and normal controls using magnetic resonance imaging. Arch Gen Psychiatry 57, 47-53.
42. Bartzokis G, Cummings J, Perlman S, Hance DB, Mintz J (1999) Increased basal ganglia iron levels in Huntington disease. Arch Neurol 56, 569-574.
43. Vymazal J, Hajek M, Patronas N, Giedd JN, Bulte JW, Baumgarner C, Tran V, Brooks RA (1995) The quantitative relation between T1-weighted and T2-weighted MRI of normal gray matter and iron concentration. J Magn Reson Imaging 5, 554-560.
44. Vymazal J, Brooks RA, Patronas N, Hajek M, Bulte JW, Di Chiro G (1995) Magnetic resonance imaging of brain iron in health and disease. J Neurol Sci 134 Suppl, 19-26.
45. Vymazal J, Zak O, Bulte JW, Aisen P, Brooks RA (1996) T1 and T2 of ferritin solutions: effect of loading factor. Magn Reson Med 36, 61-65.
46. Bulte JW, Miller GF, Vymazal J, Brooks RA, Frank JA (1997) Hepatic hemosiderosis in non-human primates: quantification of liver iron using different field strengths. Magn Reson Med 37, 530-536.
47. Stuckey R, Aldridge T, Lim FL, Moore DJ, Tinwell H, Doherty N, Davies R, Smith AG, Kimber I, Ashby J, Orphanides G, Moggs JG (2006) Induction of iron homeostasis genes during estrogen-induced uterine growth and differentiation. Mol Cell Endocrinol 253, 22-29.
48. Lavados M, Guillon M, Mujica MC, Rojo LE, Fuentes P, Maccioni RB (2008) Mild cognitive impairment and Alzheimer patients display different levels of redox-active CSF iron. J Alzheimers Dis 13, 225-232.
49. Rogers JT, Bush AI, Cho HH, Smith DH, Thomson AM, Friedlich AL, Lahiri DK, Leedman PJ, Huang X, Cahill CM (2008) Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer's disease. Biochem Soc Trans 36, 1282-1287.
50. Frackowiak J, Potempska A, Mazur-Kolecka B (2009) Formation of amyloid-beta oligomers in brain vascular smooth muscle cells transiently exposed to iron-induced oxidative stress. Acta Neuropathol 117, 557-567.
51. Kostka M, Hogen T, Danzer KM, Levin J, Habeck M, Wirth A, Wagner R, Glabe CG, Finger S, Heinzelmann U, Garidel P, Duan W, Ross CA, Kretzschmar H, Giese A (2008) Singleparticle characterization of iron-induced pore-forming alpha -synuclein oligomers. J Biol Chem 283, 10992-11003
52. Mandel SA, Amit T, Kalfon L, Reznichenko L, Weinreb O, Youdim MB (2008) Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG). J Alzheimers Dis 15, 211-222.
53. Amit T, Avramovich-Tirosh Y, Youdim MB, Mandel S (2007) Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators. FASEB J 22, 1296-1305
54. Hider RC, Ma Y, Molina-Holgado F, Gaeta A, Roy S (2008) Iron chelation as a potential therapy for neurodegenerative disease. Biochem Soc Trans 36, 1304-1308.
55. Cahill CM, Lahiri DK, Huang X, Rogers JT (2008) Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases. Biochim Biophys Acta 1790, 615-628.
56. Fleming DJ, Jacques PF, Massaro JM, D'Agostino RB, Sr., Wilson PW, Wood RJ (2001) Aspirin intake and the use of serum ferritin as a measure of iron status. Am J Clin Nutr 74, 219-226.
57. Whitfield JB, Treloar S, Zhu G, Powell LW, Martin NG (2003) Relative importance of female-specific and nonfemale- specific effects on variation in iron stores between women. Br J Haematol 120, 860-866.
58. Beard JL, Connor JR (2003) Iron Status and Neural Functioning. Annu Rev Nutr 23, 41-58.
59. Steinberg KK, Cogswell ME, Chang JC, Caudill SP, McQuillan GM, Bowman BA, Grummer-Strawn LM, Sampson EJ, Khoury MJ, Gallagher ML (2001) Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States. JAMA 285, 2216-2222.
60. Griffiths PD, Dobson BR, Jones GR, Clarke DT (1999) Iron in the basal ganglia in Parkinson's disease.An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy. Brain 122, 667-673.
61. Fleming JT, Joshi JG (1991) Ferritin: the role of aluminum in ferritin function. Neurobiol Aging 12, 413-418.
62. Collingwood JF, Mikhaylova A, Davidson M, Batich C, Streit WJ, Terry J, Dobson J (2005) In situ characterization and mapping of iron compounds in Alzheimer's disease tissue. J Alzheimers Dis 7, 267-272.
63. Collingwood JF, Chong RK, Kasama T, Cervera-Gontard L, Dunin-Borkowski RE, Perry G, Posfai M, Siedlak SL, Simpson ET, Smith MA, Dobson J (2008) Three-dimensional tomographic imaging and characterization of iron compounds within Alzheimer's plaque core material. J Alzheimers Dis 14, 235-245.
64. Kraemer HC, Yesavage JA, Taylor JL, Kupfer D (2000) How can we learn about developmental processes from crosssectional studies, or can we? Am J Psychiatry 157, 163-171.
65. Rajendran R, Minqin R, Ynsa MD, Casadesus G, Smith MA, Perry G, Halliwell B, Watt F (2009) A novel approach to the identification and quantitative elemental analysis of amyloid deposits - insights into the pathology of Alzheimer's disease. Biochem Biophys Res Commun 382, 91-95.
66. Singh A, Isaac AO, Luo X, Mohan ML, Cohen ML, Chen F, Kong Q, Bartz J, Singh N (2009) Abnormal brain iron homeostasis in human and animal prion disorders. PLoS Pathog 5, e1000336.
67. Marques F, Falcao AM, Sousa JC, Coppola G, Geschwind D, Sousa N, Correia-Neves M, Palha JA (2009) Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. Endocrinology 150, 2822-2828