Transferrin and HFE genes interact in Alzheimer's disease risk: The Epistasis Project

Neurobiology of Aging

Volumn 33, Issue 1, 2012, Pages 202.e1-202.e13

  Lehmann, Donald J ^a   Schuur, Maaike ^b   Warden, Donald R ^a   Hammond, Naomi ^c   Belbin, Olivia ^d   Kölsch, Heike ^e   Lehmann, Michael G ^a   Wilcock, Gordon K ^f,g   Brown, Kristelle ^d   Kehoe, Patrick G ^g   Morris, Chris M ^h   Barker, Rachel ^g   Coto, Eliecer ⁱ   Alvarez, Victoria ⁱ   Deloukas, Panos ^c   Mateo, Ignacio ^j   Gwilliam, Rhian ^c   Combarros, Onofre ^j   Arias Vásquez, Alejandro ^b,k   Aulchenko, Yurii S ^b   Ikram, M Arfan ^b   Breteler, Monique M ^b   van Duijn, Cornelia M ^b   Oulhaj, Abderrahim ^f   Heun, Reinhard ^e,l   Cortina Borja, Mario ^m   Morgan, Kevin ^d   Robson, Kathryn ⁿ   Smith, A David ^a   more..

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^d UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^e UNIVERSITY OF BONN   (Germany)

^f UNIVERSITY OF OXFORD   (United Kingdom)

^g UNIVERSITY OF BRISTOL   (United Kingdom)

^h NEWCASTLE UNIVERSITY   (United Kingdom)

ⁱ HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS   (Spain)

^j UNIVERSITY OF CANTABRIA   (Spain)

^k RADBOUD UNIVERSITY   (Netherlands)

^l ROYAL DERBY HOSPITAL   (United Kingdom)

^m UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁿ UNIVERSITY OF OXFORD   (United Kingdom)

more..

Author keywords

Apolipoprotein E 4; Glycosylation; Iron chelation; Microglia; Mild cognitive impairment; Neurodegeneration; Onset age; Transferrin saturation

Indexed keywords

AGE; AGED; ALZHEIMER DISEASE; APOE EPSILON4 GENE; ARTICLE; CONTROLLED STUDY; ETHNIC GROUP; EUROPEAN; GENE; GENE FREQUENCY; GENE INTERACTION; GENE LINKAGE DISEQUILIBRIUM; GENETIC RISK; HEMOCHROMATOSIS; HFE GENE; HUMAN; IRON OVERLOAD; MAJOR CLINICAL STUDY; ONSET AGE; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSFERRIN GENE;

EID: 81355123253     PISSN: 01974580     EISSN: 15581497     Source Type: Journal    
DOI: 10.1016/j.neurobiolaging.2010.07.018     Document Type: Article

References (112)

1. Aksenov M.Y., Tucker H.M., Nair P., Aksenova M.V., Butterfield D.A., Estus S., Markesbery W.R. The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease. J. Mol. Neurosci 1998, 11:151-164.
2. Alizadeh B.Z., Njajou O.T., Houwing-Duistermaat J.J., de Jong G., Vergeer J.M., Hofman A., Pols H.A., van Duijn C.M. Does bilirubin protect against hemochromatosis gene (HFE) related mortality?. Am. J. Med. Genet 2004, 129A:39-43.
3. Alizadeh B.Z., Njajou O.T., Millán M.R., Hofman A., Breteler M.M., van Duijn C.M. HFE variants, APOE and Alzheimer's disease: findings from the population-based Rotterdam study. Neurobiol. Aging 2009, 30:330-332.
4. Altamura S., Muckenthaler M.U. Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. J. Alzheimers Dis 2009, 16:879-895.
5. Amit T., Avramovich-Tirosh Y., Youdim M.B., Mandel S. Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators. FASEB J 2008, 22:1296-1305.
6. Bartzokis G., Lu P.H., Tishler T.A., Peters D.G., Kosenko A., Barrall K.A., Finn J.P., Villablanca P., Laub G., Altshuler L.L., Geschwind D.H., Mintz J., Neely E., Connor J.R. Prevalent iron metabolism gene variants associated with increased brain ferritin iron in healthy older men. J. Alzheimers Dis 2010, 20:333-341.
7. Bartzokis G., Sultzer D., Cummings J., Holt L.E., Hance D.B., Henderson V.W., Mintz J. In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging. Arch. Gen. Psychiatry 2000, 57:47-53.
8. Bartzokis G., Sultzer D., Mintz J., Holt L.E., Marx P., Phelan C.K., Marder S.R. In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI. Biol. Psychiatry 1994, 35:480-487.
9. Bartzokis G., Tishler T.A., Lu P.H., Villablanca P., Altshuler L.L., Carter M., Huang D., Edwards N., Mintz J. Brain ferritin iron may influence age- and gender-related risks of neurodegeneration. Neurobiol. Aging 2007, 28:414-423.
10. Beckman L., Beckman G. Transferrin C2 as an enhancer of cyto- and genotoxic damage. Prog. Clin. Biol. Res 1986, 209B:221-224.
11. Berg D., Hochstrasser H. Iron metabolism in Parkinsonian syndromes. Mov. Disord 2006, 21:1299-1310.
12. Bertram L., McQueen M.B., Mullin K., Blacker D., Tanzi R.E. Systematic meta-analyses of Alzheimer disease genetic association studies: the Alzgene database. Nat. Genet 2007, 39:17-23.
13. Bodovitz S., Falduto M.T., Frail D.E., Klein W.L. Iron levels modulate α-secretase cleavage of amyloid precursor protein. J. Neurochem 1995, 64:307-315.
14. Brys M., Pirraglia E., Rich K., Rolstad S., Mosconi L., Switalski R., Glodzik-Sobanska L., De Santi S., Zinkowski R., Mehta P., Praticò D., Saint Louis L.A., Wallin A., Blennow K., de Leon M.J. Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment. Neurobiol. Aging 2009, 30:682-690.
15. Butterfield D.A., Poon H.F., St Clair D., Keller J.N., Pierce W.M., Klein J.B., Markesbery W.R. Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease. Neurobiol. Dis 2006, 22:223-232.
16. Capurso C., Solfrizzi V., D'Introno A., Colacicco A.M., Capurso S.A., Mastroianni F., Liaci M., Vendemiale G., Capurso A., Panza F. The cathepsin D gene exon 2 (C224T) polymorphism and sporadic Alzheimer's disease in European populations. J. Gerontol. A Biol. Sci. Med. Sci 2005, 60:991-996.
17. Castellani R.J., Smith M.A., Nunomura A., Harris P.L., Perry G. Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?. Free Radic. Biol. Med 1999, 26:1508-1512.
18. Cecarini V., Ding Q., Keller J.N. Oxidative inactivation of the proteasome in Alzheimer's disease. Free Radic. Res 2007, 41:673-680.
19. Cleve H., Schwendner E., Rodewald A., Bidlingmaier F. Genetic transferrin types and iron-binding: a comparative study of a European and an African population sample. Hum. Genet 1988, 78:16-20.
20. Combarros O., García-Román M., Fontalba A., Fernández-Luna J.L., Llorca J., Infante J., Berciano J. 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 2003, 15:151-154.
21. Combarros O., van Duijn C.M., Hammond N., Belbin O., Arias-Vásquez A., Cortina-Borja M., Lehmann M.G., Aulchenko Y.S., Schuur M., Kölsch H., Heun R., Wilcock G.K., Brown K., Kehoe P.G., Harrison R., Coto E., Alvarez V., Deloukas P., Mateo I., Gwilliam R., Morgan K., Warden D.R., Smith A.D., Lehmann D.J. Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease. J. Neuroinflammation 2009, 6:22.
22. Connor J.R., Menzies S.L., St Martin S.M., Mufson E.J. A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains. J. Neurosci. Res 1992, 31:75-83.
23. Connor J.R., Snyder B.S., Arosio P., Loeffler D.A., LeWitt P. A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer's diseased brains. J. Neurochem 1995, 65:717-724.
24. Connor J.R., Snyder B.S., Beard J.L., Fine R.E., Mufson E.J. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. J. Neurosci. Res 1992, 31:327-335.
25. Connor J.R., Tucker P., Johnson M., Snyder B. Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer's disease. Neurosci. Lett 1993, 159:88-90.
26. Cornett C.R., Markesbery W.R., Ehmann W.D. Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. Neurotoxicology 1998, 19:339-345.
27. Cortina-Borja M., Smith A.D., Combarros O., Lehmann D.J. The synergy factor: a statistic to measure interactions in complex diseases. BMC Res. Notes 2009, 2:105.
28. Crapper McLachlan D.R., Dalton A.J., Kruck T.P., Bell M.Y., Smith W.L., Kalow W., Andrews D.F. Intramuscular desferrioxamine in patients with Alzheimer's disease. Lancet 1991, 337:1304-1308.
29. Davies P.S., Enns C.A. Expression of the hereditary hemochromatosis protein HFE increases ferritin levels by inhibiting iron export in HT29 cells. J. Biol. Chem 2004, 279:25085-25092.
30. Dedman D.J., Treffry A., Candy J.M., Taylor G.A., Morris C.M., Bloxham C.A., Perry R.H., Edwardson J.A., Harrison P.M. Iron and aluminum in relation to brain ferritin in normal individuals and Alzheimer's-disease and chronic renal-dialysis patients. Biochem. J 1992, 287:509-514.
31. Deibel M.A., Ehmann W.D., Markesbery W.R. Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: possible relation to oxidative stress. J. Neurol. Sci 1996, 143:137-142.
32. Deugnier Y., Jouanolle A.M., Chaperon J., Moirand R., Pithois C., Meyer J.F., Pouchard M., Lafraise B., Brigand A., Caserio-Schoenemann C., Mosser J., Adams P., Le Gall J.Y., David V. Gender-specific phenotypic expression and screening strategies in C282Y-linked haemochromatosis: a study of 9396 French people. Br. J. Haematol 2002, 118:1170-1178.
33. Ding B., Chen K.M., Ling H.W., Sun F., Li X., Wan T., Chai W.M., Zhang H., Zhan Y., Guan Y.J. Correlation of iron in the hippocampus with MMSE in patients with Alzheimer's disease. J. Magn. Reson. Imaging 2009, 29:793-798.
34. Ding Q., Markesbery W.R., Chen Q., Li F., Keller J.N. Ribosome dysfunction is an early event in Alzheimer's disease. J. Neurosci 2005, 25:9171-9175.
35. Drakesmith H., Sweetland E., Schimanski L., Edwards J., Cowley D., Ashraf M., Bastin J., Townsend A.R. The hemochromatosis protein HFE inhibits iron export from macrophages. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:15602-15607.
36. Dwyer B.E., Zacharski L.R., Balestra D.J., Lerner A.J., Perry G., Zhu X., Smith M.A. Getting the iron out: phlebotomy for Alzheimer's disease?. Med. Hypotheses 2009, 72:504-509.
37. Feder J.N., Penny D.M., Irrinki A., Lee V.K., Lebrón J.A., Watson N., Tsuchihashi Z., Sigal E., Bjorkman P.J., Schatzman R.C. The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:1472-1477.
38. Feder J.N., Tsuchihashi Z., Irrinki A., Lee V.K., Mapa F.A., Morikang E., Prass C.E., Starnes S.M., Wolff R.K., Parkkila S., Sly W.S., Schatzman R.C. The hemochromatosis founder mutation in HLA-H disrupts β2-microglobulin interaction and cell surface expression. J. Biol. Chem 1997, 272:14025-14028.
39. Feelders R.A., Vreugdenhil G., de Jong G., Swaak A.J., van Eijk H.G. Transferrin microheterogeneity in rheumatoid arthritis. Relation with disease activity and anemia of chronic disease. Rheumatol. Int 1992, 12:195-199.
40. Fodero L.R., Sáez-Valero J., Barquero M.S., Marcos A., McLean C.A., Small D.H. Wheat germ agglutinin-binding glycoproteins are decreased in Alzheimer's disease cerebrospinal fluid. J. Neurochem 2001, 79:1022-1026.
41. Giunta S., Galeazzi R., Valli M.B., Corder E.H., Galeazzi L. Transferrin neutralization of amyloid beta 25-35 cytotoxicity. Clin. Chim. Acta 2004, 350:129-136.
42. Good P.F., Perl D.P., Bierer L.M., Schmeidler J. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann. Neurol 1992, 31:286-292.
43. Goodman L. Alzheimer's disease: a clinico-pathologic analysis of twenty-three cases with a theory on pathogenesis. J. Nerv. Ment. Dis 1953, 117:97-129.
44. Hall E.C., Lee S.Y., Mairuae N., Simmons Z., Connor J.R. Expression of the HFE allelic variant H63D in SH-SY5Y cells affects tau phosphorylation at serine residues. Neurobiol Aging 2009, in press.
45. Hall E.C., Lee S.Y., Simmons Z., Neely E.B., Nandar W., Connor J.R. Prolyl-peptidyl isomerase, Pin1, phosphorylation is compromised in association with the expression of the HFE polymorphic allele, H63D. Biochim. Biophys. Acta 2010, 1802:389-395.
46. Hallgren B., Sourander P. The effect of age on the non-haemin iron in the human brain. J. Neurochem 1958, 3:41-51.
47. Hidalgo C., Núñez M.T. Calcium, iron and neuronal function. IUBMB Life 2007, 59:280-285.
48. Hirose W., Ikematsu K., Tsuda R. Age-associated increases in heme oxygenase-1 and ferritin immunoreactivity in the autopsied brain. Leg. Med 2003, 5(suppl 1):S360-S366.
49. Hoefkens P., Huijskes-Heins M.I., de Jeu-Jaspars C.M., van Noort W.L., van Eijk H.G. Influence of transferrin glycans on receptor binding and iron-donation. Glycoconjugate J 1997, 14:289-295.
50. Honda K., Smith M.A., Zhu X., Baus D., Merrick W.C., Tartakoff A.M., Hattier T., Harris P.L., Siedlak S.L., Fujioka H., Liu Q., Moreira P.I., Miller F.P., Nunomura A., Shimohama S., Perry G. Ribosomal RNA in Alzheimer disease is oxidized by bound redox-active iron. J. Biol. Chem 2005, 280:20978-20986.
51. Ikram M.A., Seshadri S., Bis J.C., Fornage M., DeStefano A.L., Aulchenko Y.S., Debette S., Lumley T., Folsom A.R., van den Herik E.G., Bos M.J., Beiser A., Cushman M., Launer L.J., Shahar E., Struchalin M., Du Y., Glazer N.L., Rosamond W.D., Rivadeneira F., Kelly-Hayes M., Lopez O.L., Coresh J., Hofman A., DeCarli C., Heckbert S.R., Koudstaal P.J., Yang Q., Smith N.L., Kase C.S., Rice K., Haritunians T., Roks G., de Kort P.L., Taylor K.D., de Lau L.M., Oostra B.A., Uitterlinden A.G., Rotter J.I., Boerwinkle E., Psaty B.M., Mosley T.H., van Duijn C.M., Breteler M.M., Longstreth W.T.J., Wolf P.A. Genomewide association studies of stroke. N. Engl. J. Med 2009, 360:1718-1728.
52. Jackson H.A., Carter K., Darke C., Guttridge M.G., Ravine D., Hutton R.D., Napier J.A., Worwood M. HFE mutations, iron deficiency and overload in 10,500 blood donors. Br. J. Haematol 2001, 114:474-484.
53. Jellinger K., Paulus W., Grundke-Iqbal I., Riederer P., Youdim M.B. Brain iron and ferritin in Parkinson's and Alzheimer's diseases. J. Neural Transm. Park. Dis. Dement. Sect 1990, 2:327-340.
54. Jiang D., Li X., Williams R., Patel S., Men L., Wang Y., Zhou F. Ternary complexes of iron, amyloid-beta, and nitrilotriacetic acid: binding affinities, redox properties, and relevance to iron-induced oxidative stress in Alzheimer's disease. Biochemistry 2009, 48:7939-7947.
55. Kauwe J.S., Bertelsen S., Mayo K., Cruchaga C., Abraham R., Hollingworth P., Harold D., Owen M.J., Williams J., Lovestone S., Morris J.C., Goate A.M. Suggestive synergy between genetic variants in TF and HFE as risk factors for Alzheimer's disease. Am. J. Med. Genet. B Neuropsychiatr. Genet 2010, 153B:955-959.
56. Kauwe J.S.K., Wang J., Mayo K., Morris J.C., Fagan A.M., Holtzman D.M., Goate A.M. Alzheimer's disease risk variants show association with cerebrospinal fluid amyloid beta. Neurogenetics 2009, 10:13-17.
57. Kawamata T., Tooyama I., Yamada T., Walker D.G., McGeer P.L. Lactotransferrin immunocytochemistry in Alzheimer and normal human brain. Am. J. Pathol 1993, 142:1574-1585.
58. Keller J.N., Schmitt F.A., Scheff S.W., Ding Q., Chen Q., Butterfield D.A., Markesbery W.R. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005, 64:1152-1156.
59. Kharrazi H., Vaisi-Raygani A., Rahimi Z., Tavilani H., Aminian M., Pourmotabbed T. Association between enzymatic and non-enzymatic antioxidant defense mechanism with apolipoprotein E genotypes in Alzheimer disease. Clin. Biochem 2008, 41:932-936.
60. Kivipelto M., Helkala E.L., Laakso M.P., Hanninen T., Hallikainen M., Alhainen K., Soininen H., Tuomilehto J., Nissinen A. Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study. BMJ 2001, 322:1447-1451.
61. Kuperstein F., Yavin E. Pro-apoptotic signaling in neuronal cells following iron and amyloid beta peptide neurotoxicity. J. Neurochem 2003, 86:114-125.
62. Lavados M., Guillón M., Mujica M.C., Rojo L.E., Fuentes P., Maccioni R.B. Mild cognitive impairment and Alzheimer patients display different levels of redox-active CSF iron. J. Alzheimers Dis 2008, 13:225-232.
63. Lehmann D.J., Cortina-Borja M., Warden D.R., Smith A.D., Sleegers K., Prince J.A., van Duijn C.M., Kehoe P.G. Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer's disease. Am. J. Epidemiol 2005, 162:305-317.
64. Lehmann D.J., Worwood M., Ellis R., Wimhurst V.L.J., Merryweather-Clarke A.T., Warden D.R., Smith A.D., Robson K.J.H. Iron genes, iron load and risk of Alzheimer's disease. J. Med. Genet 2006, 43:e52.
65. Loeffler D.A., Connor J.R., Juneau P.L., Snyder B.S., Kanaley L., DeMaggio A.J., Nguyen H., Brickman C.M., LeWitt P.A. Transferrin and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions. J. Neurochem 1995, 65:710-724.
66. Loeffler D.A., LeWitt P.A., Juneau P.L., Sima A.A., Nguyen H.U., DeMaggio A.J., Brickman C.M., Brewer G.J., Dick R.D., Troyer M.D., Kanaley L. Increased regional brain concentrations of ceruloplasmin in neurodegenerative disorders. Brain Res 1996, 738:265-274.
67. Lopes K.O., Sparks D.L., Streit W.J. Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity. Glia 2008, 56:1048-1060.
68. Mantyh P.W., Ghilardi J.R., Rogers S., DeMaster E., Allen C.J., Stimson E.R., Maggio J.E. Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J. Neurochem 1993, 61:1171-1174.
69. Markesbery W.R., Kryscio R.J., Lovell M.A., Morrow J.D. Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment. Ann. Neurol 2005, 58:730-735.
70. Martin W.R., Ye F.Q., Allen P.S. Increasing striatal iron content associated with normal aging. Mov. Disord 1998, 13:281-286.
71. Mason A.B., Miller M.K., Funk W.D., Banfield D.K., Savage K.J., Oliver R.W., Green B.N., MacGillivray R.T., Woodworth R.C. Expression of glycosylated and nonglycosylated human transferrin in mammalian cells. Characterization of the recombinant proteins with comparison to three commercially available transferrins. Biochemistry 1993, 32:5472-5479.
72. Mazur-Kolecka B., Dickson D., Frackowiak J. Induction of vascular amyloidosis-beta by oxidative stress depends on APOE genotype. Neurobiol. Aging 2006, 27:804-814.
73. Merryweather-Clarke A.T., Pointon J.J., Jouanolle A.M., Rochette J., Robson K.J.H. Geography of HFE C282Y and H63D mutations. Genet. Test 2000, 4:183-198.
74. Milton W.J., Atlas S.W., Lexa F.J., Mozley P.D., Gur R.E. Deep gray matter hypointensity patterns with aging in healthy adults: MR imaging at 1.5 T. Radiology 1991, 181:715-719.
75. Mitchell R.M., Lee S.Y., Simmons Z., Connor J.R. HFE polymorphisms affect cellular glutamate regulation. Neurobiol. Aging 2009, Epub ahead of print. 10.1016/j.neurobiolaging.2009.05.016.
76. Miyata M., Smith J.D. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat. Genet 1996, 14:55-61.
77. Montine T.J., Markesbery W.R., Zackert W., Sanchez S.C., Roberts L.J., Morrow J.D. The magnitude of brain lipid peroxidation correlates with the extent of degeneration but not with density of neuritic plaques or neurofibrillary tangles or with APOE genotype in Alzheimer's disease patients. Am. J. Pathol 1999, 155:863-868.
78. Montosi G., Paglia P., Garuti C., Guzman C.A., Bastin J.M., Colombo M.P., Pietrangelo A. Wild-type HFE protein normalizes transferrin iron accumulation in macrophages from subjects with hereditary hemochromatosis. Blood 2000, 96:1125-1129.
79. Morris C.M., Kerwin J.M., Edwardson J.A. Non-haem iron histochemistry of the normal and Alzheimer's disease hippocampus. Neurodegeneration 1994, 3:267-275.
80. Nunomura A., Perry G., Aliev G., Hirai K., Takeda A., Balraj E.K., Jones P.K., Ghanbari H., Wataya T., Shimohama S., Chiba S., Atwood C.S., Petersen R.B., Smith M.A. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol 2001, 60:759-767.
81. Perez L.R., Franz K.J. Minding metals: tailoring multifunctional chelating agents for neurodegenerative disease. Dalton Trans 2010, 39:2177-2187.
82. Piñero D.J., Hu J., Connor J.R. Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer's diseased brains. Cell. Mol. Biol. (Noisy-le-grand) 2000, 46:761-776.
83. Praticò D., Clark C.M., Liun F., Rokach J., Lee V.Y., Trojanowski J.Q. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch. Neurol 2002, 59:972-976.
84. Praticò D., Lee V.M.-Y., Trojanowski J.Q., Rokach J., Fitzgerald G.A. Increased F2-isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo. FASEB J 1998, 12:1777-1783.
85. Ramassamy C., Averill D., Beffert U., Bastianetto S., Theroux L., Lussier-Cacan S., Cohn J.S., Christen Y., Davignon J., Quirion R., Poirier J. Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer's disease is related to the apolipoprotein E genotype. Free Radic. Biol. Med 1999, 27:544-553.
86. Ramassamy C., Averill D., Beffert U., Theroux L., Lussier-Cacan S., Cohn J.S., Christen Y., Schoofs A., Davignon J., Poirier J. Oxidative insults are associated with apolipoprotein E genotype in Alzheimer's disease brain. Neurobiol. Dis 2000, 7:23-37.
87. Robson K.J.H., Lehmann D.J., Wimhurst V.L.C., Livesey K.J., Combrinck M., Merryweather-Clarke A.T., Warden D.R., Smith A.D. Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer's disease. J. Med. Genet 2004, 41:261-265.
88. Rogers J.T., Randall J.D., Cahill C.M., Eder P.S., Huang X., Gunshin H., Leiter L., McPhee J., Sarang S.S., Utsuki T., Greig N.H., Lahiri D.K., Tanzi R.E., Bush A.I., Giordano T., Gullans S.R. An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript. J. Biol. Chem 2002, 277:45518-45528.
89. Rottkamp C.A., Raina A.K., Zhu X., Gaier E., Bush A.I., Atwood C.S., Chevion M., Perry G., Smith M.A. Redox-active iron mediates amyloid-beta toxicity. Free Radic. Biol. Med 2001, 30:447-450.
90. Sampietro M., Caputo L., Casatta A., Meregalli M., Pellagatti A., Tagliabue J., Annoni G., Vergani C. The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease. Neurobiol. Aging 2001, 22:563-568.
91. Sayre L.M., Perry G., Harris P.L., Liu Y., Schubert K.A., Smith M.A. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals. J. Neurochem 2000, 74:270-279.
92. Schenck J.F., Zimmerman E.A., Li Z., Adak S., Saha A., Tandon R., Fish K.M., Belden C., Gillen R.W., Barba A., Henderson D.L., Neil W., O'Keefe T. High-field magnetic resonance imaging of brain iron in Alzheimer disease. Top. Magn. Reson. Imaging 2006, 17:41-50.
93. Schjeide B.M., McQueen M.B., Mullin K., DiVito J., Hogan M.F., Parkinson M., Hooli B., Lange C., Blacker D., Tanzi R.E., Bertram L. Assessment of Alzheimer's disease case-control associations using family-based methods. Neurogenetics 2009, 10:19-25.
94. Schubert D., Chevion M. The role of iron in β amyloid toxicity. Biochem. Biophys. Res. Commun 1995, 216:702-707.
95. Sikström C., Beckman L., Hallmans G., Asplund K. Transferrin types, iron-binding capacity and body iron stores. Hum. Hered 1993, 43:337-341.
96. Skoog I., Lernfelt B., Landahl S., Palmertz B., Andreasson L.A., Nilsson L., Persson G., Odén A., Svanborg A. 15-year longitudinal study of blood pressure and dementia. Lancet 1996, 347:1141-1145.
97. Smith M.A., Zhu X., Tabaton M., Liu G., McKeel D.W., Cohen M.L., Wang X., Siedlak S.L., Dwyer B.E., Hayashi T., Nakamura M., Nunomura A., Perry G. Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. J. Alzheimers Dis 2010, 19:363-372.
98. Solomon A., Kivipelto M., Wolozin B., Zhou J., Whitmer R.A. Midlife serum cholesterol and increased risk of Alzheimer's and vascular dementia three decades later. Dement. Geriatr. Cogn. Disord 2009, 28:75-80.
99. Streit W.J., Miller K.R., Lopes K.O., Njie E. Microglial degeneration in the aging brain - bad news for neurons?. Front. Biosci 2008, 13:3423-3438.
100. Tamaoka A., Miyatake F., Matsuno S., Ishii K., Nagase S., Sahara N., Ono S., Mori H., Wakabayashi K., Tsuji S., Takahashi H., Shoji S. Apolipoprotein E allele-dependent antioxidant activity in brains with Alzheimer's disease. Neurology 2000, 54:2319-2321.
101. Taniguchi M., Okayama Y., Hashimoto Y., Kitaura M., Jimbo D., Wakutani Y., Wada-Isoe K., Nakashima K., Akatsu H., Furukawa K., Arai H., Urakami K. Sugar chains of cerebrospinal fluid transferrin as a new biological marker of Alzheimer's disease. Dement. Geriatr. Cogn. Disord 2008, 26:117-122.
102. Terni B., Boada J., Portero-Otin M., Pamplona R., Ferrer I. Mitochondrial ATP-synthase in the entorhinal cortex is a target of oxidative stress at stages I/II of Alzheimer's disease pathology. Brain Pathol 2010, 20:222-233.
103. Van Landeghem G.F., Sikström C., Beckman L.E., Adolfsson R., Beckman L. Transferrin C2, metal binding and Alzheimer's disease. Neuroreport 1998, 9:177-179.
104. van Rensburg S.J., Berman P., Potocnik F., MacGregor P., Hon D., de Villiers N. 5- and 6-glycosylation of transferrin in patients with Alzheimer's disease. Metab. Brain Dis 2004, 19:89-96.
105. van Rensburg S.J., Carstens M.E., Potocnik F.C.V., Aucamp A.K., Taljaard J.J.F. Increased frequency of the transferrin C2 subtype in Alzheimer's disease. Neuroreport 1993, 4:1269-1271.
106. Wang J., Markesbery W.R., Lovell M.A. Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. J. Neurochem 2006, 96:825-832.
107. Williams T.I., Lynn B.C., Markesbery W.R., Lovell M.A. Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer's disease. Neurobiol. Aging 2006, 27:1094-1099.
108. Wong C.T., Saha N. Effects of transferrin genetic phenotypes on total iron-binding capacity. Acta Haematol 1986, 75:215-218.
109. Yu H.L., Chertkow H.M., Bergman H., Schipper H.M. Aberrant profiles of native and oxidized glycoproteins in Alzheimer plasma. Proteomics 2003, 3:2240-2248.
110. Zatta P., Messori L., Mauri P., van Rensburg S.J., van Zyl J., Gabrielli S., Gabbiani C. The C2 variant of human serum transferrin retains the iron binding properties of the native protein. Biochim. Biophys. Acta 2005, 1741:264-270.
111. Zhang A.S., Davies P.S., Carlson H.L., Enns C.A. Mechanisms of HFE-induced regulation of iron homeostasis: insights from the W81A HFE mutation. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:9500-9505.
112. Zhu W.Z., Zhong W.D., Wang W., Zhan C.J., Wang C.Y., Qi J.P., Wang J.Z., Lei T. Quantitative MR phase-corrected imaging to investigate increased brain iron deposition of patients with Alzheimer disease. Radiology 2009, 253:497-504.