Perturbed iron distribution in Alzheimer's disease serum, cerebrospinal fluid, and selected brain regions: A systematic review and meta-analysis

Journal of Alzheimer's Disease

Volumn 42, Issue 2, 2014, Pages 679-690

  Tao, Yunlong ^a,b   Wang, Yu ^c   Rogers, Jack T ^d   Wang, Fudi ^a  

^a ZHEJIANG UNIVERSITY   (China)

^b INSTITUTE OF GEOLOGY AND GEOPHYSICS   (China)

^c MAX PLANCK INSTITUTE   (Germany)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Alzheimer's disease; cerebrospinal fluid; iron; iron overload; meta analysis; serum iron; systematic review

Indexed keywords

IRON;

ALZHEIMER DISEASE; AMYGDALOID NUCLEUS; ARTICLE; BRAIN LEVEL; BRAIN REGION; CAUDATE NUCLEUS; CEREBELLUM; CEREBROSPINAL FLUID LEVEL; CINGULATE GYRUS; FRONTAL LOBE; GLOBUS PALLIDUS; HIPPOCAMPUS; HISTOCHEMISTRY; HUMAN; IRON BLOOD LEVEL; IRON INTAKE; PARIETAL LOBE; PUTAMEN; SUBSTANTIA NIGRA; SYSTEMATIC REVIEW; TEMPORAL LOBE; THALAMUS; BLOOD; BRAIN; CEREBROSPINAL FLUID; IRON METABOLISM DISORDER; META ANALYSIS; METABOLISM; PATHOLOGY;

ALZHEIMER DISEASE; BRAIN; HUMANS; IRON; IRON METABOLISM DISORDERS;

EID: 84916882462     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-140396     Document Type: Article

References (91)

1. Smith MA, Harris PLR, Sayre LM, Perry G (1997) Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci U S A 94, 9866-9868.
2. Hentze MW, Muckenthaler MU, Galy B, Camaschella C (2010) Two to tango: Regulation of mammalian iron metabolism. Cell 142, 24-38.
3. De Domenico I, Ward DM, Kaplan J (2008) Regulation of iron acquisition and storage: Consequences for iron-linked disorders. Nat Rev Mol Cell Biol 9, 72-81.
4. Grunblatt E, Bartl J, Riederer P (2011) The link between iron, metabolic syndrome, and Alzheimer's disease. J Neural Transm 118, 371-379.
5. Perry G, Sayre LM, Atwood CS, Castellani RJ, Cash AD, Rottkamp CA, Smith MA (2002) The role of iron and copper in the aetiology of neurodegenerative disorders: Therapeutic implications. CNS Drugs 16, 339-352.
6. Smith MA, Zhu X, Tabaton M, Liu G, McKeelDW, Jr., 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.
7. Smith MA, Perry G (1995) Free radical damage, iron, and Alzheimer's disease. J Neurol Sci 134(Suppl), 92-94.
8. Sayre LM, Perry G, Atwood CS, SmithMA(2000) The role of metals in neurodegenerative diseases. Cell Mol Biol (Noisyle- grand) 46, 731-741.
9. Perry G, Taddeo MA, Petersen RB, Castellani RJ, Harris PL, Siedlak SL, Cash AD, Liu Q, Nunomura A,Atwood CS, Smith MA(2003) Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease. Biometals 16, 77-81.
10. Castellani RJ, Moreira PI, Liu G, Dobson J, Perry G, Smith MA, Zhu X (2007) Iron: The redox-active center of oxidative stress in Alzheimer disease. Neurochem Res 32, 1640-1645.
11. Magaki S, Raghavan R, Mueller C, Oberg KC, Vinters HV, Kirsch WM (2007) Iron, copper, and iron regulatory protein 2 in Alzheimer's disease and related dementias. Neurosci Lett 418, 72-76.
12. Good PF, Perl DP, Bierer LM, Schmeidler J (1992) Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: A laser microprobe (LAMMA) study. Ann Neurol 31, 286-292.
13. Dedman DJ, Treffry A, Candy JM, Taylor GA, Morris CM, Bloxham CA, Perry RH, Edwardson JA, Harrison PM (1992) Iron and aluminium in relation to brain ferritin in normal individuals and Alzheimer's-disease and chronic renal-dialysis patients. Biochem J 287(Pt 2), 509-514.
14. Connor JR, Snyder BS, Beard JL, Fine RE, Mufson EJ (1992) Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. J Neurosci Res 31, 327-335.
15. LeVine SM (1997) Iron deposits in multiple sclerosis and Alzheimer's disease brains. Brain Res 760, 298-303.
16. Smith MA, Harris PL, Sayre LM, Perry G (1997) Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc Natl Acad Sci U S A 94, 9866-9868.
17. Rogers JT, Randall JD, Cahill CM, Eder PS, Huang X, Gunshin H, Leiter L, McPhee J, Sarang SS, Utsuki T, Greig NH, Lahiri DK,Tanzi RE, Bush AI, GiordanoT, GullansSR(2002) An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript. J Biol Chem 277, 45518-45528.
18. Cho HH, Cahill CM, Vanderburg CR, Scherzer CR,Wang B, Huang X, Rogers JT (2010) Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1. J Biol Chem 285, 31217-31232.
19. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI (2010) Iron-export ferroxidase activity of beta-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell 142, 857-867.
20. Pulliam JF, Jennings CD, Kryscio RJ, Davis DG, Wilson D, Montine TJ, Schmitt FA,MarkesberyWR(2003) Association ofHFEmutations with neurodegeneration and oxidative stress in Alzheimer's disease and correlation with APOE. Am J Med Genet B Neuropsychiatr Genet 119B 48-53.
21. Robson KJ, Lehmann DJ, Wimhurst VL, Livesey KJ, Combrinck M, Merryweather-Clarke AT, Warden DR, Smith AD (2004) 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 41, 261-265.
22. Connor JR, Lee SY (2006) HFE mutations and Alzheimer's disease. J Alzheimers Dis 10, 267-276.
23. Wang Y, Xu S, Liu Z, Lai C, Xie Z, Zhao C, Wei Y, Bi JZ (2013) Meta-analysis on the association between the TF gene rs1049296 and AD. Can J Neurol Sci 40, 691-697.
24. Todorich BM, Connor JR (2004) Redox metals in Alzheimer's disease. Ann N Y Acad Sci 1012, 171-178.
25. Thompson KJ, Shoham S, Connor JR (2001) Iron and neurodegenerative disorders. Brain Res Bull 55, 155-164.
26. Greenough MA, Camakaris J, Bush AI (2013) Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Neurochem Int 62, 540-555.
27. Plantin LO, Lyingtunell U, Kristensson K (1987) Traceelements in the human central-nervous-system studied with neutron-activation analysis. Biol Trace Elem Res 13, 69-75.
28. Thompson CM, Markesbery WR, Ehmann WD, Mao YX, Vance DE (1988) Regional brain trace-element studies in Alzheimer's disease. Neurotoxicology 9, 1-7.
29. Wenstrup D, Ehmann WD, Markesbery WR (1990) Trace element imbalances in isolated subcellular fractions of Alzheimer's disease brains. Brain Res 533, 125-131.
30. Corrigan FM, Reynolds GP, Ward NI (1993) Hippocampal tin, aluminum and zinc in Alzheimer's disease. Biometals 6, 149-154.
31. Griffiths PD, Crossman AR (1993) Distribution of iron in the basal ganglia and neocortex in postmortem tissue in Parkinson's disease and Alzheimer's disease. Dementia 4, 61-65.
32. Loeffler DA, Connor JR, Juneau PL, Snyder BS, Kanaley L, DeMaggio AJ, Nguyen H, Brickman CM, LeWitt PA (1995) Transferrin and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions. J Neurochem 65, 710-724.
33. Samudralwar DL, Diprete CC, Ni BF, Ehmann WD,Markesbery WR (1995) Elemental imbalances in the olfactory pathway in Alzheimer's disease. J Neurol Sci 130, 139-145.
34. Deibel MA, Ehmann WD, Markesbery WR (1996) Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer's disease: Possible relation to oxidative stress. J Neurol Sci 143, 137-142.
35. Stedman JD, Spyrou NM (1997) Elemental analysis of the frontal lobe of "normal" brain tissue and that affected by Alzheimer's disease. J Radioanalytical Nucl Chem 217, 163-166.
36. Cornett CR, Ehmann WD, Wekstein DR, Markesbery WR (1998) Trace elements in Alzheimer's disease pituitary glands. Biol Trace Elem Res 62, 107-114.
37. Cornett CR, Markesbery WR, Ehmann WD (1998) Imbalances of trace elements related to oxidative damage in Alzheimer's disease brain. Neurotoxicology 19, 339-345.
38. Gu M, Owen AD, Toffa SE, Cooper JM, Dexter DT, Jenner P, Marsden CD, Schapira AH (1998) Mitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases. J Neurol Sci 158, 24-29.
39. Prasher VP, Gosling P, Blair J (1998) Role of iron in Alzheimer-type dementia in Down syndrome. Int J Geriatr Psychiatry 13, 818-819.
40. Andrasi E, Farkas E, Gawlik D, Rosick U, Bratter P (2000) Brain iron and zinc contents of German patients with Alzheimer disease. J Alzheimers Dis 2, 17-26.
41. Panayi AE, SpyrouNM,Part P (2001) Differences in trace element concentrations between Alzheimer and "normal" human brain tissue using instrumental neutron activation analysis (INAA). J Radioanalytical Nucl Chem 249, 437-441.
42. House MJ, St Pierre TG, Kowdley KV, Montine T, Connor J, Beard J, Berger J, Siddaiah N, Shankland E, Jin LW (2007) Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients. Magn Reson Med 57, 172-180.
43. House MJ, St Pierre TG, McLean C (2008) 1.4T study of proton magnetic relaxation rates, iron concentrations, and plaque burden in Alzheimer's disease and control postmortem brain tissue. Magn Reson Med 60, 41-52.
44. Galazka-Friedman J, Bauminger ER, Szlachta K, Friedman A (2012) The role of iron in neurodegeneration- Mossbauer spectroscopy, electron microscopy, enzyme linked immunosorbent assay and neuroimaging studies. J Phys Condens Matter 24, 244106.
45. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci 158, 47-52.
46. Schrag M, Mueller C, Oyoyo U, Smith MA, Kirsch WM (2011) Iron, zinc and copper in the Alzheimer's disease brain: A quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion. Prog Neurobiol 94, 296-306.
47. Srivastava RA, Jain JC (2002) Scavenger receptor classBtype I expression and elemental analysis in cerebellum and parietal cortex regions of the Alzheimer's disease brain. J Neurol Sci 196, 45-52.
48. Qin Y, Zhu W, Zhan C, Zhao L, Wang J, Tian Q, Wang W (2011) Investigation on positive correlation of increased brain iron deposition with cognitive impairment in Alzheimer disease by using quantitativeMRR2' mapping. J Huazhong Univ Sci Technolog Med Sci 31, 578-585.
49. Schrag M, Dickson A, Jiffry A, Kirsch D, Vinters HV, Kirsch W(2010) The effect of formalin fixation on the levels of brain transition metals in archived samples. Biometals 23, 1123-1127.
50. Squitti R, Pasqualetti P, Polimanti R, Salustri C, Moffa F, Cassetta E, Lupoi D, Ventriglia M, Cortesi M, Siotto M, Vernieri F, Rossini PM (2013) Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease. Curr Alzheimer Res 10, 191-198.
51. Huang CW, Wang SJ, Wu SJ, Yang CC, Huang MW, Lin CH, Cheng IH (2013) Potential blood biomarker for disease severity in the taiwanese population with Alzheimer's disease. Am J Alzheimers Dis Other Demen 28, 75-83.
52. Mueller C, Schrag M, Crofton A, Stolte J, Muckenthaler MU, Magaki S, Kirsch W (2012) Altered serum iron and copper homeostasis predicts cognitive decline in mild cognitive impairment. J Alzheimers Dis 29, 341-350.
53. Giambattistelli F, Bucossi S, Salustri C, Panetta V, Mariani S, Siotto M, Ventriglia M, Vernieri F, Dell'acqua ML, Cassetta E, Rossini PM, Squitti R (2012) Effects of hemochromatosis and transferrin gene mutations on iron dyshomeostasis, liver dysfunction and on the risk of Alzheimer's disease. Neurobiol Aging 33, 1633-1641.
54. Torsdottir G, Kristinsson J, Snaedal J, Johannesson T (2011) Ceruloplasmin and iron proteins in the serum of patients with Alzheimer's disease. Dement Geriatr Cogn Dis Extra 1, 366-371.
55. Squitti R, Ghidoni R, Scrascia F, Benussi L, Panetta V, Pasqualetti P, Moffa F, Bernardini S, Ventriglia M, Binetti G, Rossini PM (2011) Free copper distinguishes mild cognitive impairment subjects from healthy elderly individuals. J Alzheimers Dis 23, 239-248.
56. Hozumi I, Hasegawa T, Honda A, Ozawa K, Hayashi Y, Hashimoto K, Yamada M, Koumura A, Sakurai T, Kimura A, Tanaka Y, Satoh M, Inuzuka T (2011) Patterns of levels of biological metals in CSF differ among neurodegenerative diseases. J Neurol Sci 303, 95-99.
57. Vural H, Demirin H, Kara Y, Eren I, Delibas N (2010) Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer's disease. J Trace Elem Med Biol 24, 169-173.
58. Squitti R, Salustri C, Siotto M,Ventriglia M,Vernieri F, Lupoi D, Cassetta E, Rossini PM (2010) Ceruloplasmin/transferrin ratio changes in Alzheimer's disease. Int J Alzheimers Dis 2011, 231595.
59. Milward EA, Bruce DG, KnuimanMW,Divitini ML, Cole M, Inderjeeth CA, Clarnette RM, Maier G, Jablensky A, Olynyk JK (2010) A cross-sectional community study of serum iron measures and cognitive status in older adults. J Alzheimers Dis 20, 617-623.
60. Baum L, Chan IH, Cheung SK, Goggins WB, Mok V, Lam L, Leung V, Hui E, Ng C, Woo J, Chiu HF, Zee BC, Cheng W, Chan MH, Szeto S, Lui V, Tsoh J, Bush AI, Lam CW, Kwok T (2010) Serum zinc is decreased in Alzheimer's disease and serum arsenic correlates positively with cognitive ability. Biometals 23, 173-179.
61. Gerhardsson L, Blennow K, Lundh T, Londos E, Minthon L (2009) Concentrations of metals, beta-amyloid and taumarkers in cerebrospinal fluid in patients with Alzheimer's disease. Dement Geriatr Cogn Disord 28, 88-94.
62. Bostrom F, Hansson O, Gerhardsson L, Lundh T, Minthon L, Stomrud E, ZetterbergH, Londos E (2009) CSF Mg and Ca as diagnostic markers for dementia with Lewy bodies. Neurobiol Aging 30, 1265-1271.
63. 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.
64. Gerhardsson L, Lundh T, Minthon L, Londos E (2008) Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer's disease. Dement Geriatr Cogn Disord 25, 508-515.
65. Squitti R, Ventriglia M, Barbati G, Cassetta E, Ferreri F, Dal Forno G, Ramires S, Zappasodi F, Rossini PM (2007) 'Free' copper in serum of Alzheimer's disease patients correlates with markers of liver function. J Neural Transm 114, 1589-1594.
66. Alimonti A, Ristori G, Giubilei F, Stazi MA, Pino A, Visconti A, Brescianini S, Sepe Monti M, Forte G, Stanzione P, Bocca B, Bomboi G, D'Ippolito C, Annibali V, Salvetti M, Sancesario G (2007) Serum chemical elements and oxidative status in Alzheimer's disease, Parkinson disease and multiple sclerosis. Neurotoxicology 28, 450-456.
67. Bocca B, Forte G, Petrucci F, Pino A, Marchione F, Bomboi G, Senofonte O, Giubilei F, Alimonti A (2005) Monitoring of chemical elements and oxidative damage in patients affected by Alzheimer's disease. Ann Ist Super Sanita 41, 197-203.
68. Squitti R, Rossini PM, Cassetta E, Moffa F, Pasqualetti P, Cortesi M, Colloca A, Rossi L, Finazzi-Agro A (2002) dpenicillamine reduces serum oxidative stress in Alzheimer's disease patients. Eur J Clin Invest 32, 51-59.
69. Squitti R, Lupoi D, Pasqualetti P, Dal Forno G, Vernieri F, Chiovenda P, Rossi L, Cortesi M, Cassetta E, Rossini PM (2002) Elevation of serum copper levels in Alzheimer's disease. Neurology 59, 1153-1161.
70. Ozcankaya R, Delibas N (2002) Malondialdehyde, superoxide dismutase, melatonin, iron, copper, and zinc blood concentrations in patients with Alzheimer disease: Crosssectional study. Croat Med J 43, 28-32.
71. Molina JA, Jimenez-Jimenez FJ, Aguilar MV, Meseguer I, Mateos-Vega CJ, Gonzalez-Munoz MJ, de Bustos F, Porta J, Orti-Pareja M, Zurdo M, Barrios E, Martinez-Para MC (1998) Cerebrospinal fluid levels of transition metals in patients with Alzheimer's disease. J Neural Transm 105, 479-488.
72. Molaschi M, Ponzetto M, Bertacna B, Berrino E, Ferrario E (1996) Determination of selected trace elements in patients affected by dementia. Arch Gerontol Geriatr 22(Suppl 1), 39-42.
73. Religa D, Strozyk D, Cherny RA, Volitakis I, Haroutunian V, Winblad B, Naslund J, Bush AI (2006) Elevated cortical zinc in Alzheimer disease. Neurology 67, 69-75.
74. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P (2000) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses. http://www.ohri.ca/programs/clinical epidemiology /oxford.asp.
75. Bandyopadhyay S, Rogers JT (2014) Alzheimer's disease therapeutics targeted to the control of amyloid precursor protein translation: Maintenance of brain iron homeostasis. Biochem Pharmacol 88, 486-494.
76. Crespo AC, Silva B, Marques L, Marcelino E, Maruta C, Costa S, Timoteo A, Vilares A, Couto FS, Faustino P, Correia AP, Verdelho A, Porto G, Guerreiro M, Herrero A, Costa C, de Mendonca A, Costa L, Martins M (2014) Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation. Neurobiol Aging 35, 777-785.
77. Bonda DJ, Lee HG, Blair JA, Zhu X, Perry G, Smith MA (2011) Role of metal dyshomeostasis in Alzheimer's disease. Metallomics 3, 267-270.
78. Honda K, Casadesus G, Petersen RB, Perry G, Smith MA (2004) Oxidative stress and redox-active iron in Alzheimer's disease. Ann N Y Acad Sci 1012, 179-182.
79. Rolston RK, Perry G, Zhu X, Castellani RJ, Dwyer BE, Lee HG, Petersen RB, Smith MA (2009) Iron: A Pathological Mediator of Alzheimer Disease? Agro Food Ind Hi Tech 19, 33-36.
80. Ward NI, Mason JA (1987) Neutron-activation analysis techniques for identifying elemental status in Alzheimer's disease. J Radioanalytical Nucl Chem 113, 515-526.
81. Connor JR, Menzies SL, St Martin SM, Mufson EJ (1992) A histochemical study of iron, transferrin, and ferritin in Alzheimer's diseased brains. J Neurosci Res 31, 75-83.
82. Jellinger K, Paulus W, Grundke-Iqbal I, Riederer P, Youdim MB (1990) Brain iron and ferritin in Parkinson's and Alzheimer's diseases. J Neural Transm Park Dis Dement Sect 2, 327-340.
83. Bartzokis G,TishlerTA, Shin IS, Lu PH, Cummings JL (2004) Brain ferritin iron as a risk factor for age at onset in neurodegenerative diseases. Ann N Y Acad Sci 1012, 224-236.
84. Bartzokis G, Tishler TA (2000) MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease. Cell Mol Biol (Noisy-le-grand) 46, 821-833.
85. Bartzokis G, Sultzer D, Mintz J, Holt LE, Marx P, Phelan CK, Marder SR (1994) In vivo evaluation of brain iron in Alzheimer's disease and normal subjects using MRI. Biol Psychiatry 35, 480-487.
86. Bartzokis G, Sultzer D, Cummings J, Holt LE, Hance DB, Henderson VW, Mintz J (2000) In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging. Arch Gen Psychiatry 57, 47-53.
87. Zhu WZ, Zhong WD, Wang W, Zhan CJ, Wang CY, Qi JP, Wang JZ, Lei T (2009) Quantitative MR phase-corrected imaging to investigate increased brain iron deposition of patients with Alzheimer disease. Radiology 253, 497-504.
88. Blakemore SJ, Frith U (2005) The learning brain: Lessons for education: A precis. Dev Sci 8, 459-465.
89. Kromer Vogt LJ, Hyman BT, Van Hoesen GW, Damasio AR (1990) Pathological alterations in the amygdala in Alzheimer's disease. Neuroscience 37, 377-385.
90. de Jong LW, van der Hiele K, Veer IM, Houwing JJ, Westendorp RG, Bollen EL, de Bruin PW, Middelkoop HA, van Buchem MA, van der Grond J (2008) Strongly reduced volumes of putamen and thalamus in Alzheimer's disease: An MRI study. Brain 131, 3277-3285.
91. Noble JH, Jr (2006) Meta-analysis: Methods, strengths, weaknesses, and political uses. J Lab Clin Med 147, 7-20.