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Size Fractionation of Metal Species from Serum Samples for Studying Element Biodistribution in Alzheimer’s Disease

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Metals in the Brain

Part of the book series: Neuromethods ((NM,volume 124))

Abstract

This work considers the development of a novel analytical procedure for rapid and simple size fractionation of metal species from human serum samples, with a great potential for studying characteristic abnormalities of metal homeostasis associated with Alzheimer’s disease and other neurodegenerative disorders. For this purpose, serum samples are subjected to protein precipitation under non-denaturing conditions, taking special care for maintaining the integrity of metal–biomolecule bindings and for preventing species transformation, and then both the supernatant (low molecular mass fraction) and the precipitate (high molecular mass fraction) are analyzed by ICP-MS in order to determine the biodistribution of serum trace elements. This methodology is validated for 11 trace elements, including aluminum, cadmium, cobalt, chromium, copper, iron, manganese, molybdenum, selenium, vanadium, and zinc, in terms of sensitivity, selectivity, accuracy, and precision.

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Abbreviations

Aβ:

Amyloid β

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

HMM:

High molecular mass

ICP-MS:

Inductively coupled plasma mass spectrometry

LMM:

Low molecular mass

LOD:

Limit of detection

MCI:

Mild cognitive impairment

PCA:

Principal component analysis

PLS-DA:

Partial least squares discriminant analysis

RSD:

Relative standard deviation

References

  1. Lobinski R, Becker JS, Haraguchi H, Sarkar B (2010) Metallomics: guidelines for terminology and critical evaluation of analytical chemistry approaches (IUPAC Technical Report). Pure Appl Chem 82:493–504

    Article  CAS  Google Scholar 

  2. Haraguchi H (2004) Metallomics as integrated biometal science. J Anal At Spectrom 19:5–14

    Article  CAS  Google Scholar 

  3. Valko M, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208

    Article  CAS  PubMed  Google Scholar 

  4. Bolognin S, Messori L, Zatta P (2009) Metal ion physiopathology in neurodegenerative disorders. Neuromolecular Med 11:223–238

    Article  CAS  PubMed  Google Scholar 

  5. Sayre LM, Perry G, Atwood CS, Smith MA (2000) The role of metals in neurodegenerative diseases. Cell Mol Biol 46:731–741

    CAS  PubMed  Google Scholar 

  6. Kozlowski H, Luczkowski M, Remelli M, Valensin D (2012) Copper, zinc and iron in neurodegenerative diseases (Alzheimer’s, Parkinson’s and prion diseases). Coord Chem Rev 256:2129–2141

    Article  CAS  Google Scholar 

  7. Tomljenovic L (2011) Aluminum and Alzheimer’s disease: After a century of controversy, is there a plausible link? J Alzheimers Dis 23:567–598

    CAS  PubMed  Google Scholar 

  8. Charlet L, Chapron Y, Faller P, Kirsch R, Stone AT, Baveye PC (2012) Neurodegenerative diseases and exposure to the environmental metals Mn, Pb, and Hg. Coord Chem Rev 256:2147–2163

    Article  CAS  Google Scholar 

  9. Reitz C, Brayne C, Mayeux R (2011) Epidemiology of Alzheimer disease. Nat Rev Neurol 7:137–152

    Article  PubMed  PubMed Central  Google Scholar 

  10. Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer's disease. Lancet 368:387–403

    Article  CAS  PubMed  Google Scholar 

  11. Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med 23:134–147

    Article  CAS  PubMed  Google Scholar 

  12. Tuppo EE, Arias HR (2005) The role of inflammation in Alzheimer's disease. Int J Biochem Cell Biol 37:289–305

    Article  CAS  PubMed  Google Scholar 

  13. Squitti R (2012) Metals in Alzheimer’s disease: a systemic perspective. Front Biosci 17:451–472

    Article  CAS  Google Scholar 

  14. 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

    Article  CAS  PubMed  Google Scholar 

  15. Bush AI, Pettingell WH, Multhaup G, Paradis M, Vonsattel JP, Gusella JF, Beyreuther K, Masters CL, Tanzi RE (1994) Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265:1464–1467

    Article  CAS  PubMed  Google Scholar 

  16. Hesse L, Beher D, Masters CL, Multhaup G (1994) The βA4 amyloid precursor protein binding to copper. FEBS Lett 349:109–116

    Article  CAS  PubMed  Google Scholar 

  17. Egaña JT, Zambrano C, Nuñez MT, Gonzalez-Billault C, Maccioni RB (2003) Iron-induced oxidative stress modify tau phosphorylation patterns in hippocampal cell cultures. Biometals 16:215–223

    Article  PubMed  Google Scholar 

  18. Zhou LX, Du JT, Zeng ZY, Wu WH, Zhao YF, Kanazawa K, Ishizuka Y, Nemoto T, Nakanishi H, Li YM (2007) Copper (II) modulates in vitro aggregation of a tau peptide. Peptides 28:2229–2234

    Article  CAS  PubMed  Google Scholar 

  19. Perry G, Cash AD, Srinivas R, Smith MA (2002) Metals and oxidative homeostasis in Alzheimer’s disease. Drug Dev Res 56:293–299

    Article  CAS  Google Scholar 

  20. Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87

    Article  CAS  PubMed  Google Scholar 

  21. Crapper DR, Krishnan SS, Dalton AJ (1973) Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Science 180:511–513

    Article  CAS  PubMed  Google Scholar 

  22. Loef M, Schrauzer GN, Walach H (2011) Selenium and Alzheimer’s disease: a systematic review. J Alzheimers Dis 26:81–104

    CAS  PubMed  Google Scholar 

  23. Cuajungco MP, Fagét KY (2003) Zinc takes the center stage: its paradoxical role in Alzheimer’s disease. Brain Res Rev 41:44–56

    Article  CAS  PubMed  Google Scholar 

  24. Cornett CR, Markesbery WR, Ehmann WD (1998) Imbalances of trace elements related to oxidative damage in Alzheimer’s disease brain. Neurotoxicology 19:339–345

    CAS  PubMed  Google Scholar 

  25. Rao JKS, Rao RV, Shanmugavelu P, Menon RB (1999) Trace elements in Alzheimer’s disease brain: a new hypothesis. Alzheimers Rep 2:241–246

    Google Scholar 

  26. González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2014) Characterization of metal profiles in serum during the progression of Alzheimer’s disease. Metallomics 9:292–300

    Article  Google Scholar 

  27. González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2014) Homeostasis of metals in the progression of Alzheimer’s disease. Biometals 27:539–549

    Article  PubMed  CAS  Google Scholar 

  28. Rao KSJ, Shanmugavelu P, Shankar SK, Devi RPR, Rao RV, Pande S, Menon RB (1999) Trace elements in the cerebrospinal fluid in Alzheimer's disease. Alzheimers Rep 2:333–338

    Google Scholar 

  29. Basun H, Forssell LG, Wetterberg L, Winblad B (1991) Metals and trace-elements in plasma and cerebrospinal-fluis in normal aging and Alzheimer’s disease. J Neural Transm Park Dis Dement Sect 3:231–258

    CAS  PubMed  Google Scholar 

  30. 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

    CAS  PubMed  Google Scholar 

  31. 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

    Article  CAS  PubMed  Google Scholar 

  32. 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

    Article  CAS  PubMed  Google Scholar 

  33. Molina JA, Jiménez-Jiménez FJ, Aguilar MV, Meseguer I, Mateos-Vega CJ, González-Muñoz MJ, de Bustos F, Porta J, Ortí-Pareja M, Zurdo M, Barrios E, Martínez-Para MC (1998) Cerebrospinal fluid levels of transition metals in patients with Alzheimer’s disease. J Neural Transm 105:479–488

    Article  CAS  PubMed  Google Scholar 

  34. Kovatsi L, Touliou K, Tsolaki M, Kazis A (2006) Cerebrospinal fluid levels of calcium, magnesium, copper and zinc in patients with Alzheimer’s disease and mild cognitive impairment. J Trace Elem Electrolytes 23:247–250

    Article  CAS  Google Scholar 

  35. 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

    Article  CAS  PubMed  Google Scholar 

  36. Smorgon C, Mari E, Atti AR, Dalla Nora E, Zamboni PF, Calzoni F, Passaro A, Fellin R (2004) Trace elements and cognitive impairment: an elderly cohort study. Arch Gerontol Geriatr Suppl 9:393–402

    Article  CAS  Google Scholar 

  37. 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

    Article  CAS  PubMed  Google Scholar 

  38. Kozlowski H, Janicka-Klos A, Brasun J, Gaggelli E, Valensin D, Valensin G (2009) Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation). Coord Chem Rev 253:2665–2685

    Article  CAS  Google Scholar 

  39. Yokel RA (2006) Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration. J Alzheimers Dis 10:223–253

    PubMed  Google Scholar 

  40. Rivera-Mancía S, Ríos C, Montes S (2011) Manganese accumulation in the CNS and associated pathologies. Biometals 24:811–825

    Article  PubMed  CAS  Google Scholar 

  41. Andrási E, Farkas E, Scheibler H, Réffy A, Bezúr L (1995) Al, Zn, Cu, Mn and Fe levels in brain in Alzheimer’s disease. Arch Gerontol Geriatr 21:89–97

    Article  PubMed  Google Scholar 

  42. Srivastava RAK, Jain JC (2002) Scavenger receptor class B type I expression and elemental analysis in cerebellum and parietal cortex regions of the Alzheimer’s disease brain. J Neurol Sci 196:45–52

    Article  CAS  PubMed  Google Scholar 

  43. 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

    Article  CAS  PubMed  Google Scholar 

  44. Bocca B, Alimonti A, Bomboi G, Giubilei F, Forte G (2006) Alterations in the level of trace metals in Alzheimer's disease. J Trace Elem Electrolytes 23:270–276

    Article  CAS  Google Scholar 

  45. Jolly DH, Pointrinal P, Millart H, Kariger E, Blanchard F, Collery P, Choisy H (1993) Blood zinc, magnesium, calcium, aluminum and manganese concentrations in patients, with or without Alzheimer-type dementia. Trace Elem Med 10:192–195

    Google Scholar 

  46. Zatta P, Cervellin D, Mattiello G, Gerotto M, Lazzari F, Gasparoni G, Gomirato L, Mazzolini G, Scarpa G, Zanoboni V, Pilone G, Favarato M (1993) Plasma multielemental analysis in Alzheimer’s disease and multi-infarctual dementia. Trace Elem Med 10:85–89

    Google Scholar 

  47. Omar RA, Chyan YJ, Andorn AD, Poeggeler B, Robakis NK, Pappolla MA (1999) Increased expression but reduced activity of antioxidant enzymes in Alzheimer’s disease. J Alzheimers Dis 1:139–145

    CAS  PubMed  Google Scholar 

  48. Vural H, Sirin B, Yilmaz N, Eren I, Delibas N (2009) The role of arginine–nitric oxide pathway in patients with Alzheimer disease. Biol Trace Elem Res 129:58–64

    Article  CAS  PubMed  Google Scholar 

  49. Cutts DA, Maguire RP, Stedman JD, Leenders KL, Spyrou NM (1999) A comparative study in Alzheimer’s and normal brains of trace element distribution using PIXE and INA analyses and glucose metabolism by positron emission tomography. Biol Trace Elem Res 71:541–549

    Article  PubMed  Google Scholar 

  50. Stedman JD, Spyrou NM (1997) Elemental analysis of the frontal lobe of “normal” brain tissue and that affected by Alzheimer’s disease. J Radioanal Nucl Chem 217:163–166

    Article  CAS  Google Scholar 

  51. Leite RE, Jacob-Filho W, Saiki M, Grinberg LT, Ferretti RE (2008) Determination of trace elements in human brain tissues using neutron activation analysis. J Radioanal Nucl Chem 278:581–584

    Article  CAS  Google Scholar 

  52. Cardoso BR, Ong TP, Jacob-Filho W, Jaluul O, Freitas MI, Cozzolino SM (2010) Nutritional status of selenium in Alzheimer’s disease patients. Br J Nutr 103:803–806

    Article  CAS  PubMed  Google Scholar 

  53. Giacoppo S, Galuppo M, Calabrò RS, D'Aleo G, Marra A, Sessa E, Bua DG, Potortì AG, Dugo G, Bramanti P, Mazzon E (2014) Heavy metals and neurodegenerative diseases: an observational study. Biol Trace Elem Res 161:151–160

    Article  CAS  PubMed  Google Scholar 

  54. Duce JA, Bush AI (2010) Biological metals and Alzheimer’s disease: implications for therapeutics and diagnostics. Prog Neurobiol 92:1–18

    Article  CAS  PubMed  Google Scholar 

  55. Gong G, O’Bryant SE (2010) The arsenic exposure hypothesis for Alzheimer disease. Alzheimer Dis Assoc Disord 24:311–316

    Article  CAS  PubMed  Google Scholar 

  56. Mutter J, Curth A, Naumann J, Deth R, Walach H (2010) Does inorganic mercury play a role in Alzheimer’s disease? A systematic review and an integrated molecular mechanism. J Alzheimers Dis 22:357–374

    CAS  PubMed  Google Scholar 

  57. Webster WS, Valois AA (1981) The toxic effects of cadmium on the neonatal mouse CNS. J Neuropathol Exp Neurol 40:247–257

    Article  CAS  PubMed  Google Scholar 

  58. Costa L, Fox D (1983) A selective decrease of cholinergic muscarinic receptors in the visual cortex of adult rats following developmental lead exposure. Brain Res 276:259–266

    Article  CAS  PubMed  Google Scholar 

  59. Zapatero MD, de Jalon AG, Pascual F, Calvo ML, Escanero J, Marro A (1995) Serum aluminum levels in Alzheimer’s disease and other senile dementias. Biol Trace Elem Res 47:235–240

    Article  CAS  PubMed  Google Scholar 

  60. Thompson CM, Markesbery WR, Ehmann WD, Mao YX, Vance DE (1988) Regional brain trace-element studies in Alzheimer’s disease. Neurotoxicology 9:1–7

    CAS  PubMed  Google Scholar 

  61. Templeton DM (1999) Biomedical aspects of trace element speciation. Fresenius J Anal Chem 363:505–511

    Article  CAS  Google Scholar 

  62. Williams RJP (2001) Chemical selection of elements by cells. Coord Chem Rev 216-217:583–595

    Article  CAS  Google Scholar 

  63. Mounicou S, Szpunar J, Lobinski R (2009) Metallomics: the concept and methodology. Chem Soc Rev 38:1119–1138

    Article  CAS  PubMed  Google Scholar 

  64. Szpunar J (2000) Advances in analytical methodology for bioinorganic speciation analysis: metallomics, metalloproteomics and heteroatom-tagged proteomics and metabolomics. Analyst 125:963–988

    Article  CAS  PubMed  Google Scholar 

  65. Lobinski R (2001) Characterizing speciation of trace elements in the chemistry of life. Fresenius J Anal Chem 369:113–114

    Article  CAS  PubMed  Google Scholar 

  66. Issaq HJ (2001) The role of separation science in proteomics research. Electrophoresis 22:3629–3638

    Article  CAS  PubMed  Google Scholar 

  67. Rabilloud T, Chevallet M, Luche S, Lelong C (2010) Two-dimensional gel electrophoresis in proteomics: past, present and future. J Proteomics 73:2064–2077

    Article  CAS  PubMed  Google Scholar 

  68. Behne D, Kyriakopoulos A (2001) Mammalian selenium-containing proteins. Annu Rev Nutr 21:453–473

    Article  CAS  PubMed  Google Scholar 

  69. Bouyssiere B, Szpunar J, Lobinski R (2002) Gas chromatography with inductively coupled plasma mass spectrometric detection in speciation analysis. Spectrochim Acta B 57:805–828

    Article  Google Scholar 

  70. Montes-Bayón M, DeNicola K, Caruso JA (2003) Liquid chromatography-inductively coupled plasma mass spectrometry. J Chromatogr A 1000:457–476

    Article  PubMed  CAS  Google Scholar 

  71. Alvarez-Llamas G, Fernández de la Campa MR, Sanz-Medel A (2005) ICP-MS for specific detection in capillary electrophoresis. Trends Anal Chem 24:28–36

    Article  CAS  Google Scholar 

  72. Nischwitz V, Berthele A, Michalke B (2010) Rapid size fractionation of metal species in paired human serum and cerebrospinal fluid samples using ultrafiltration with off-line element selective detection. J Anal At Spectrom 25:1130–1137

    Article  CAS  Google Scholar 

  73. Polak TB, Milacic R, Mitrovic B, Benedik M (2001) Speciation of low molecular weight Al complexes in serum of CAPD patients. J Pharm Biomed Anal 26:189–201

    Article  CAS  PubMed  Google Scholar 

  74. Mota AM, Simaes-Goncalves ML (1996) Direct methods of speciation of heavy metals in natural waters. In: Caroli S (ed) Element speciation in bioorganic chemistry. Wiley, New York

    Google Scholar 

  75. Scopes RK (1994) Protein purification: principles and practice. Springer Advanced Texts in Chemistry, New York, pp 85–92

    Book  Google Scholar 

  76. Simpson RJ (2004) Purifying proteins for proteomics: a laboratory manual. Cold Spring Harbor Laboratory Press, New York, pp 721–722

    Google Scholar 

  77. Jakubowski N, Lobinski R, Moens L (2004) Metallobiomolecules. The basis of life, the challenge of atomic spectroscopy. J Anal At Spectrom 19:1–4

    Article  CAS  Google Scholar 

  78. Garcia JS, Magalhães CS, Arruda MA (2006) Trends in metal-binding and metalloprotein analysis. Talanta 69:1–15

    Article  CAS  PubMed  Google Scholar 

  79. Gao Y, Chen C, Chai ZF (2007) Advanced nuclear analytical techniques for metalloproteomics. J Anal At Spectrom 22:856–866

    Article  CAS  Google Scholar 

  80. Mounicou S, Szpunar J, Lobinski R (2010) Inductively-coupled plasma mass spectrometry in proteomics, metabolomics and metallomics studies. Eur J Mass Spectrom (Chichester) 16:243–253

    Article  CAS  Google Scholar 

  81. Svantesson E, Pettersson J, Markides KE (2002) The use of inorganic elemental standards in the quantification of proteins and biomolecular compounds by inductively coupled plasma spectrometry. J Anal At Spectrom 17:491–496

    Article  CAS  Google Scholar 

  82. Tanner SD, Baranov VI, Bandura DR (2002) Reaction cells and collision cells for ICP-MS: a tutorial review. Spectrochim Acta B 57:1361–1452

    Article  Google Scholar 

  83. Michalke B (2002) The coupling of LC to ICP-MS in element speciation: I. General aspects. Trends Anal Chem 21:142–153

    Article  CAS  Google Scholar 

  84. McKahnn G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 34:939–944

    Article  Google Scholar 

  85. Petersen RC (2004) Mild cognitive impairment as a diagnostic entity. J Intern Med 256:183–194

    Article  CAS  PubMed  Google Scholar 

  86. Muñiz CS, Fernández-Martin JL, Marchante-Gayón JM, Alonso IG, Cannata-Andía JB, Sanz-Medel A (2001) Reference values for trace and ultratrace elements in human serum determined by double-focusing ICP-MS. Biol Trace Elem Res 82:259–272

    Article  PubMed  Google Scholar 

  87. Daszykowski M, Walczak B, Massart DL (2003) Projection methods in chemistry. Chemometr Intell Lab 65:97–112

    Article  CAS  Google Scholar 

  88. van den Berg RA, Hoefsloot HCJ, Westerhuis JA, Smilde AK, van der Werf MJ (2006) Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics 7:142

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Seiler HG, Sigel A, Sigel H (1994) Handbook on metals in clinical and analytical chemistry. Marcel Dekker, New York

    Google Scholar 

  90. Hegde ML, Shanmugavelu P, Vengamma B, Rao TS, Menon RB, Rao RV, Rao KSJ (2004) Serum trace element levels and the complexity of inter-element relations in patients with Parkinson’s disease. J Trace Elem Med Biol 18:163–171

    Article  CAS  PubMed  Google Scholar 

  91. Mustak MS, Rao TSS, Shanmugavelu P, Sundar NMS, Menon RB, Rao RV, Rao KSJ (2008) Assessment of serum macro and trace element homeostasis and the complexity of inter-element relations in bipolar mood disorders. Clin Chim Acta 394:47–53

    Article  CAS  PubMed  Google Scholar 

  92. Kiziler AR, Aydemir B, Guzel S, Alici B, Ataus S, Tuna MB, Durak H, Kilic M (2010) May the level and ratio changes of trace elements be utilized in identification of disease progression and grade in prostatic cancer? J Trace Elem Electrolytes 27:65–72

    Article  CAS  Google Scholar 

  93. Caroli S, Alimonti A, Coni E, Petrucci F, Senofonte O, Violante N (1994) The assessment of reference values for elements in human biological tissues and fluids: a systematic review. Crit Rev Anal Chem 24:363–398

    Article  CAS  Google Scholar 

  94. Alimonti A, Bocca B, Mannella E, Petrucci F, Zennaro F, Cotichini R, D'Ippolito C, Agresti A, Caimi S, Forte G (2005) Assessment of reference values for selected elements in a healthy urban population. Ann Ist Super Sanita 41:181–187

    CAS  PubMed  Google Scholar 

  95. Sanz-Medel A, Soldado Cabezuelo AB, Milačič R, Bantan Polak T (2002) The chemical speciation of aluminium in human serum. Coord Chem Rev 228:373–383

    Article  CAS  Google Scholar 

  96. Simonsen LO, Harbak H, Bennekou P (2012) Cobalt metabolism and toxicology – a brief update. Sci Total Environ 432:210–215

    Article  CAS  PubMed  Google Scholar 

  97. Nischwitz V, Berthele A, Michalke B (2008) Speciation analysis of selected metals and determination of their total contents in paired serum and cerebrospinal fluid samples: an approach to investigate the permeability of the human blood-cerebrospinal fluid-barrier. Anal Chim Acta 627:258–269

    Article  CAS  PubMed  Google Scholar 

  98. Kokarnig S, Tsirigotaki A, Wiesenhofer T, Lackner V, Francesconi KA, Pergantis SA, Kuehnelt D (2015) Concurrent quantitative HPLC-mass spectrometry profiling of small selenium species in human serum and urine after ingestion of selenium supplements. J Trace Elem Med Biol 29:83–90

    Article  CAS  PubMed  Google Scholar 

  99. De Blas BI, Sanz Castro R, López Riquelme N, Tormo Díaz C, Apraiz Goyenaga D (2007) Optimization of the trace element determination by ICP-MS in human blood serum. J Trace Elem Med Biol 21:14–17

    Article  CAS  Google Scholar 

  100. Frank EL, Hughes MP, Bankson DD, Roberts WL (2001) Effects of anticoagulants and contemporary blood collection containers on aluminum, copper, and zinc results. Clin Chem 47:1109–1112

    CAS  PubMed  Google Scholar 

  101. Dombovari J, Varga Z, Becker JS, Matyus J, Kakuk G, Papp L (2001) ICP-MS determination of trace elements in the serum samples of healthy subjects using different sample preparation methods. Atom Spectrosc 22:331–335

    CAS  Google Scholar 

  102. Bocca B, Alimonti A, Forte G, Petrucci F, Pirola C, Senofonte O, Violante N (2003) High-throughput microwave-digestion procedures to monitor neurotoxic elements in body fluids by means of inductively coupled plasma mass spectrometry. Anal Bioanal Chem 377:65–70

    Article  CAS  PubMed  Google Scholar 

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González-Domínguez, R. (2017). Size Fractionation of Metal Species from Serum Samples for Studying Element Biodistribution in Alzheimer’s Disease. In: White, A. (eds) Metals in the Brain. Neuromethods, vol 124. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6918-0_8

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  • DOI: https://doi.org/10.1007/978-1-4939-6918-0_8

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