Metallomics pp 21-37 | Cite as

Metallomics Applied to the Study of Neurodegenerative and Mental Diseases

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1055)


Biochemical imbalances, provoked by aging or a secondary illness, might directly affect the brain, causing severe problems, such as loss of memory or alteration of behavior patterns. Brain disorders are usually classified as injuries (such as stroke, hematomas, and concussions), tumors, and neurodegenerative (such as Parkinson’s and Alzheimer’s diseases) and mental (such as depression, bipolar disorder, schizophrenia) diseases. As the pathophysiology of these illnesses is not completely established and multiple factors are involved, metallomics, a bioanalytical strategy that allows the detection of metal ions and metalloproteins in diverse biological matrices, is of extreme relevance in identifying which elements are affected by a disease and/or treatment. Thus, determining which element ions suffer disturbances in their homeostasis during the disease progress is relevant to understand the biochemical changes and propose new drug targets. In addition, it is well known that oxidative stress plays an important role in the development of pathological neurodegenerative and mental diseases, which may be caused by metal ion dyshomeostasis, so it is also important to understand endogenous antioxidant metalloprotein and metalloenzyme mechanisms in this regard. In this context, recent applications of metallomics in the study of neurodegenerative and mental disorders are discussed in this chapter, as well as future trends in this research area.


Metallomics Brain Mass spectrometry imaging ICP-MS Neurodegenerative diseases Mental disorders Metalloproteins Metalloenzymes Oxidative stress 





Atomic absorption spectrometry


Alzheimer’s disease


Amyotrophic lateral sclerosis



Bipolar disorder


Central nervous system


Cerebrospinal fluid


Huntington’s disease


Inductively coupled plasma mass spectrometry


Laser ablation inductively coupled plasma mass spectrometry




Magnetic resonance imaging


Multiple sclerosis




Parkinson’s disease


Superoxide dismutase


Wilson’s disease


  1. Abdalla DS, Monteiro HP, Oliveira JA, Bechara E (1986) Activities of superoxide dismutase and glutathione peroxidase in schizophrenic and manic-depressive patients. Clin Chem 32(5):805–807PubMedPubMedCentralGoogle Scholar
  2. Ahmed SSSJ, Santosh W (2010) Metallomic profiling and linkage map analysis of early Parkinson’s disease: a new insight to aluminum marker for the possible diagnosis. PLoS One 5(6):e11252PubMedPubMedCentralCrossRefGoogle Scholar
  3. Arinola G, Idonije B, Akinlade K, Ihenyen O (2010) Essential trace metals and heavy metals in newly diagnosed schizophrenic patients and those on anti-psychotic medication. J Res Med Sci 15(5):245–249PubMedPubMedCentralGoogle Scholar
  4. Arnal N, Cristalli DO, de Alaniz MJT, Marra C (2010) Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives. Brain Res 1319:118–130PubMedCrossRefPubMedCentralGoogle Scholar
  5. Aschner M (1996) The functional significance of brain metallothioneins. FASEB J 10(10):1129–1136PubMedCrossRefPubMedCentralGoogle Scholar
  6. Ayton S, Lei P, Duce JA, Wong BX, Sedjahtera A, Adlard PA, Bush AI, Finkelstein DI (2013) Ceruloplasmin dysfunction and therapeutic potential for Parkinson disease. Ann Neurol 73:554–559PubMedCrossRefPubMedCentralGoogle Scholar
  7. Barbariga M, Curnis F, Andolfo A, Zanardi A, Lazzaro M, Conti A, Magnani G, Volontè MA, Ferrari L, Comi G, Corti A, Alessio M (2015) Ceruloplasmin functional changes in Parkinson’s disease-cerebrospinal fluid. Mol Neurodegener 10:59PubMedPubMedCentralCrossRefGoogle Scholar
  8. Barnham KJ, Bush AI (2014) Biological metals and metal-targeting compounds in major neurodegenerative disorders. Chem Soc Rev 43:6727–6749PubMedCrossRefPubMedCentralGoogle Scholar
  9. Basun H, Forssell LG, Wetterberg L, Winblad B (1991) Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer’s disease. J Neural Transm Park Dis Dement Sect 3:231–258PubMedPubMedCentralGoogle Scholar
  10. Bharucha KJ, Friedman JK, Vincent AS, Ross ED (2009) Lower serum ceruloplasmin levels correlate with younger age of onset in Parkinson’s disease. J Neurol 255(12):1957–1962CrossRefGoogle Scholar
  11. Blennow K, Zetterberg H (2009) Cerebrospinal fluid biomarkers for Alzheimer’s disease. J Alzheimers Dis 18:413–417PubMedCrossRefPubMedCentralGoogle Scholar
  12. Blom ES, Giedraitis V, Zetterberg H, Fukumoto H, Blennow K, Hyman BT, Irizarry MC, Wahlund LO, Lannfelt L, Ingelsson M (2009) Rapid progression from mild cognitive impairment to Alzheimer’s disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dement Geriatr Cogn Disord 27:458–464PubMedCrossRefPubMedCentralGoogle Scholar
  13. Boaru SG, Merle U, Uerlings R, Zimmermann A, Weiskirchen S, Matusch A, Stremmel W, Weiskirchen R (2014) Simultaneous monitoring of cerebral metal accumulation in an experimental model of Wilson’s disease by laser ablation inductively coupled plasma mass spectrometry. BMC Neurosci 15:98–111PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bocca B, Alimonti A, Petrucci F, Violante N, Sancesario G, Forte G, Senofonte O (2004) Quantification of trace elements by sector field inductively coupled plasma mass spectrometry in urine, serum, blood and cerebrospinal fluid of patients with Parkinson’s disease. Spectrochim Acta B 59:559–566CrossRefGoogle Scholar
  15. Bolann BJ, Khazen-Rahil R, Henriksen H, Isrenn R, Ulvik RJ (2007) Evaluation of methods for trace-element determination with emphasis on their usability in the clinical routine laboratory. Scand J Clin Lab Invest 67(4):353–366PubMedCrossRefGoogle Scholar
  16. Boll MC, Alcaraz-Zubeldia M, Montes S, Rios C (2008) Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NO(x) content in the CSF. A different marker profile in four neurodegenerative diseases. Neurochem Res 33:1717–1723PubMedCrossRefPubMedCentralGoogle Scholar
  17. Bonilla E, Estevez J, Suarez H, Morales LM, Chacin de Bonilla L, Villalobos R, D'Avila JO (1991) Serum ferritin deficiency in Huntington’s disease patients. Neurosci Lett 129:22–24PubMedCrossRefPubMedCentralGoogle Scholar
  18. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259PubMedPubMedCentralCrossRefGoogle Scholar
  19. Brown JSJ (1994) Role of selenium and other trace elements in the geography of schizophrenia. Schizophr Bull 20:387–398PubMedCrossRefPubMedCentralGoogle Scholar
  20. Chahine L, Stern M, Chen-Plotkin A (2014) Blood-based biomarkers for Parkinson’s disease. Parkinsonism Relat Disord 20(1):S99–S103PubMedPubMedCentralCrossRefGoogle Scholar
  21. Cristóvão JS, Santos R, Gomes CM (2016) Metals and neuronal metal binding proteins implicated in Alzheimer’s disease. Oxidative Med Cell Longev 2016:1–13CrossRefGoogle Scholar
  22. Crouch PJ, Barnham KJ (2012) Therapeutic redistribution of metal ions to treat Alzheimer’s disease. Acc Chem Res 45:1604–1611PubMedCrossRefGoogle Scholar
  23. Ebadi M, Sharma S (2006) Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease. Exp Biol Med 231(9):1576–1583CrossRefGoogle Scholar
  24. El-Agnaf OM, Salem SA, Paleologou KE, Cooper LJ, Fullwood NJ, Gibson MJ, Curran MD, Court JA, Mann DM, Ikeda S, Cookson MR, Hardy J, Allsop D (2003) Alpha-synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma. FASEB J 17:1945–1947Google Scholar
  25. Fattal O, Budur K, Vaughan AJ, Franco K (2006) Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics 47(1):1–7PubMedCrossRefPubMedCentralGoogle Scholar
  26. Ferenci P (2004) Diagnosis and current therapy of Wilson’s disease. Aliment Pharmacol Ther 19(2):157–165PubMedCrossRefPubMedCentralGoogle Scholar
  27. Forte G, Bocca B, Senofonte O, Petrucci F, Brusa L, Stanzione P, Zannino S, Violante N, Alimonti A, Sancesario G (2004) Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of patients with Parkinson’s disease. J Neural Transm 111:1031–1040PubMedCrossRefPubMedCentralGoogle Scholar
  28. Fukushima T, Tan X, Luo Y, Wang P, Song J, Kanda H, Hayakawa T, Kumagai T, Kakamu T, Tsuji M, Hidaka T, Mori Y (2013) Heavy metals in blood and urine and its relation to depressive symptoms in Parkinson’s disease patients. Fukushima J Med Sci 59(2):76–80PubMedCrossRefGoogle Scholar
  29. Gama CS, Salvador M, Andreazza AC, Kapczinski F, Silva Belmonte-de-Abreu P (2006) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in schizophrenia: a study of patients treated with haloperidol or clozapine. Prog Neuro-Psychopharmacol Biol Psychiatry 30(3):512–515CrossRefGoogle Scholar
  30. 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 25:508–515PubMedCrossRefPubMedCentralGoogle Scholar
  31. Goldfischer S, Sternlieb I (1968) Changes in the distribution of hepatic copper in relation to the progression of Wilson’s disease (hepatolenticular degeneration). Am J Pathol 53:883–901PubMedPubMedCentralGoogle Scholar
  32. González-Domínguez R, García-Barrera T, Gómez-Ariza JL (2014) Characterization of metal profiles in serum during the progression of Alzheimer’s disease. Metallomics 6:292–300PubMedCrossRefPubMedCentralGoogle Scholar
  33. González-Estecha M, Trasobares EM, Tajima K, Cano S, Fernández C, López JL, Unzeta B, Arroyo M, Fuentenebro F (2011) Trace elements in bipolar disorder. J Trace Elem Med Biol 25(1):S78–S83PubMedCrossRefPubMedCentralGoogle Scholar
  34. Halliwell B (2001) Role of free radicals in the neurodegenerative diseases. Drugs Aging 18:685–716PubMedCrossRefPubMedCentralGoogle Scholar
  35. Halliwell B (2006) Phagocyte-derived reactive species: salvation or suicide? Trends Biochem Sci 31(9):509–515PubMedCrossRefPubMedCentralGoogle Scholar
  36. Hampel H, Burger K, Teipel S, Bokde A, Zetterberg H, Blennow K (2008) Core candidate neurochemical and imaging biomarkers of Alzheimer’s disease. Alzheimers Dement 4:38–48PubMedCrossRefPubMedCentralGoogle Scholar
  37. Hands SL, Mason R, Sajjad MU, Giorgini F, Wyttenbach A (2010) Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington’s disease. Biochem Soc Trans 38(2):552–558PubMedCrossRefPubMedCentralGoogle Scholar
  38. Hare DJ, Kysenius K, Paul B, Knauer B, Hutchinson RW, O’Connor C, … Doble PA (2017). Imaging Metals in Brain Tissue by Laser Ablation - Inductively Coupled Plasma - Mass Spectrometry (LA-ICP-MS). J Vis Exp 22(119) 55042. Advance online publication. Google Scholar
  39. He J, Qiao JP, Zhu S, Xue M, Chen W, Wang X, Tempier A, Huang Q, Kong J, Li XM (2013) Serum β-amyloid peptide levels spike in the early stage of Alzheimer-like plaque pathology in an APP/PS1 double transgenic mouse model. Curr Alzheimer Res 10(9):979–986PubMedCrossRefPubMedCentralGoogle Scholar
  40. Hutchinson RW, Cox AG, McLeod C, Marshall P, Harper A, Dawson EL, Howlett DR (2005) Imaging and spatial distribution of beta-amyloid peptide and metal ions in Alzheimer's plaques by laser ablation-inductively coupled plasma-mass spectrometry. Anal Biochem 346:225–233PubMedCrossRefPubMedCentralGoogle Scholar
  41. Ihara Y, Chuda D, Kuroda S, Haybara T (1999) Hydroxyl radical and superoxide dismutase in blood of patients with Parkinson's disease: relationship to clinical data. J Neurol Sci 170(2):90–95PubMedCrossRefPubMedCentralGoogle Scholar
  42. Jin L, Wang J, Zhao L, Jin H, Fei G, Zhang Y, Zeng M, Zhong C (2011) Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson's disease. Brain 134:50–58PubMedCrossRefPubMedCentralGoogle Scholar
  43. Kim H-J (2013) Alpha-Synuclein expression in patients with Parkinson’s disease: a Clinician’s perspective. Exp Neurol 22(2):77–83Google Scholar
  44. Kosaka T, Imagawa M, Seki K, Arai H, Sasaki H, Tsuji S, Asami-Odaka A, Fukushima T, Imai K, Iwatsubo T (1997) The beta APP717 Alzheimer mutation increases the percentage of plasma amyloid-beta protein ending at A beta42(43). Neurology 48:741–745PubMedCrossRefPubMedCentralGoogle Scholar
  45. Kunz M, Gama CS, Andreazza AC, Salvador M, Cereser KM, Gomes FA, Belmonte-de-Abreu PS, Berk M, Kapczinski F (2008) Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 32(7):1677–1681CrossRefGoogle Scholar
  46. Lee JY, Kim JH, Choi DW, Lee DW, Park JH, Yoon HJ, Pyo HS, Kwon HJ, Park KS (2012) The association of heavy metal of blood and serum in the Alzheimer’s diseases. Toxicol Res 28(2):93–98PubMedPubMedCentralCrossRefGoogle Scholar
  47. Lee PH, Lee G, Park HJ, Bang OY, Joo IS, Huh K (2006) The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy. J Neural Transm 113:1435–1439PubMedCrossRefPubMedCentralGoogle Scholar
  48. Lee Y-H, Wong DT (2009) Saliva: an emerging biofluid for early detection of diseases. Am J Dent 22(4):241–248PubMedPubMedCentralGoogle Scholar
  49. Li QX, Mok SS, Laughton KM, McLean CA, Cappai R, Masters CL, Culvenor JG, Horne MK (2007) Plasma alpha-synuclein is decreased in subjects with Parkinson’s disease. Exp Neurol 204:583–588PubMedCrossRefPubMedCentralGoogle Scholar
  50. Loeffier 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 65:710–716CrossRefGoogle Scholar
  51. Maeda S, Sahara N, Saito Y, Murayama M, Yoshiike Y, Kim H, Miyasaka T, Murayama S, Ikai A, Takashima A (2007) Granular tau oligomers as intermediates of tau filaments. Biochemistry 46(12):3856–3861PubMedCrossRefPubMedCentralGoogle Scholar
  52. Manto M (2014) Abnormal copper homeostasis: mechanisms and roles in neurodegeneration. Toxics 2:27–345CrossRefGoogle Scholar
  53. Marklund SL (1982) Human copper-containing superoxide dismutase of high molecular weight. Proc Natl Acad Sci U S A 79(24):7634–7638PubMedPubMedCentralCrossRefGoogle Scholar
  54. Martínez-Hernández R, Montes S, Higuera-Calleja J, Yescas P, Boll MC, Diaz-Ruiz A, Rios C (2011) Plasma ceruloplasmin ferroxidase activity correlates with the nigral sonographic area in Parkinson’s disease patients: a pilot study. Neurochem Res 36:2111–2115PubMedCrossRefPubMedCentralGoogle Scholar
  55. Matusch A, Depboylu C, Palm C, Wu B, Höglinger GU, Schäfer KH, Becker JS (2010) Cerebral bioimaging of Cu, Fe, Zn, and Mn in the MPTP mouse model of Parkinson’s disease using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). J Am Soc Mass Spectrom 21:161–171PubMedCrossRefPubMedCentralGoogle Scholar
  56. Matusch A, Fenn LS, Depboylu C, Klietz M, Strohmer S, McLean JA, Becker JS (2012) Combined elemental and biomolecular mass spectrometry imaging (MSI) for probing the inventory of tissue at a micrometer scale. Anal Chem 84:3170–3178PubMedPubMedCentralCrossRefGoogle Scholar
  57. Mehta PD, Pirttila T, Mehta SP, Sersen EA, Aisen PS, Wisniewski HM (2000) Plasma and cerebrospinal fluid levels of amyloid beta proteins 1-40 and 1-42 in Alzheimer disease. Arch Neurol 57:100–105PubMedCrossRefPubMedCentralGoogle Scholar
  58. Michael GJ, Esmailzadeh S, Moran LB, Christian L, Pearce RKB, Graeber MB (2011) Up-regulation of metallothionein gene expression in Parkinsonian astrocytes. Neurogenetics 12(4):295–305PubMedCrossRefPubMedCentralGoogle Scholar
  59. Molina J, Jiménez-Jiménez F, Aguilar M, 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 105:479–488PubMedCrossRefPubMedCentralGoogle Scholar
  60. Morrison PJ, Nevin NC (1994) Serum iron, total iron binding capacity and ferritin in early Huntington disease patients. Ir J Med Sci 163:236–237PubMedCrossRefPubMedCentralGoogle Scholar
  61. Mukerjee S, Mahadik SP, Scheffer R, Correnti EE, Kelkar H (1996) Impaired antioxidant defense at the onset of psychosis. Schizophr Res 19(1):19–26PubMedCrossRefPubMedCentralGoogle Scholar
  62. Mulder TP, Janssens AR, Verspaget HW, van Hattum J, Lamers CB (1992) Metallothionein concentration in the liver of patients with Wilson’s disease, primary biliary cirrhosis, and liver metastasis of colorectal cancer. J Hepatol 16(3):346–350PubMedCrossRefPubMedCentralGoogle Scholar
  63. Muller M, Leavitt BR (2014) Iron dysregulation in Huntington’s disease. J Neurochem 130:328–350PubMedCrossRefPubMedCentralGoogle Scholar
  64. Murphy MP, LeVine H (2010) Alzheimer’s disease and the β-amyloid peptide. J Alzheimers Dis 19(1):311–327PubMedPubMedCentralCrossRefGoogle Scholar
  65. Nartey NO, Frei JV, Cherian MG (1987) Hepatic copper and metallothionein distribution in Wilson’s disease (hepatolenticular degeneration). Lab Investig 57(4):397–401PubMedPubMedCentralGoogle Scholar
  66. Nawaz R, Zahir E, Siddiqui S, Usmani A, Shad KF (2014) The role of trace metals and environmental factors in the onset and progression of schizophrenia in Pakistani population. World J Neurosci 4:450–460CrossRefGoogle Scholar
  67. Ogihara H, Ogihara T, Miki M, Yasuda H, Mino M (1995) Plasma copper and antioxidant status in Wilson’s disease. Pediatr Res 37(2):219–226PubMedCrossRefPubMedCentralGoogle Scholar
  68. Olatunbosun DA, Akindele MO, Adadevoh BK, Asuni T (1975) Serum copper in schizophrenia in Nigerians. Br J Psychiatry 127:191–121CrossRefGoogle Scholar
  69. Orisakwe OE (2014) The role of lead and cadmium in psychiatry. N Am J Med Sci 6(8):370–376PubMedPubMedCentralCrossRefGoogle Scholar
  70. Park JH, Lee DW, Park KS (2014) Elevated serum copper and ceruloplasmin levels in Alzheimer’s disease. Asia-Pacific Psychiatry 6(1):38–45PubMedCrossRefPubMedCentralGoogle Scholar
  71. Pomara N, Willoughby LM, Sidtis JJ, Mehta PD (2005) Selective reductions in plasma Abeta 1-42 in healthy elderly subjects during longitudinal follow-up: a preliminary report. Am J Geriatr Psychiatr 13:914–917Google Scholar
  72. Prakash A, Dhaliwal GK, Kumar P, Majeed AB (2017) Brain biometals and Alzheimer’s disease - boon or bane? Int J Neurosci 127:99–108PubMedCrossRefPubMedCentralGoogle Scholar
  73. Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, Wagh UV, Debsikdar VB, Mahadik SP (2003) Decreased antioxidant enzymes and membrane essential poly- unsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res 121(2):109–122PubMedCrossRefPubMedCentralGoogle Scholar
  74. Rasia RM, Bertoncini CW, Marsh D, Hpyser W, Cherny D, Zweckstetter M, Griesinger C, Jovin TM, Fernández CO (2005) Structural characterization of copper(II) binding to α-synuclein: insights into the bioinorganic chemistry of Parkinson's disease. Proc Natl Acad Sci U S A 102(12):4294–4299PubMedPubMedCentralCrossRefGoogle Scholar
  75. Rodriguez-Castro KI, Hevia-Urrutia FJ, Sturniolo GC (2015) Wilson’s disease: a review of what we have learned. World J Hepatol 7(29):2859–2870PubMedPubMedCentralCrossRefGoogle Scholar
  76. Rohani M, Jalali N, Khademolhosseini M, Miri S, Shahidi GA, Ghourchian S (2013) Serum ceruloplasmin and ferritin levels in patients with Parkinson’s disease. Mov Disord 28:893Google Scholar
  77. Samgard K, Zetterberg H, Blennow K, Hansson O, Minthon L, Londos E (2010) Cerebrospinal fluid total tau as a marker of Alzheimer’s disease intensity. Int J Geriatr Psychiatry 25:403–410PubMedCrossRefPubMedCentralGoogle Scholar
  78. Sanyal J, Shiek SSJ, Ng HKT, Naiya T, Ghosh E, Banerjee TK, Lakshmi J, Guha G, Rao VR (2016) Metallomic biomarkers in cerebrospinal fluid and serum in patients with Parkinson’s disease in Indian population. Sci Rep 6:35097PubMedPubMedCentralCrossRefGoogle Scholar
  79. Sas K, Robotka H, Toldi J, Vécsei L (2007) Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci 257:221–239PubMedCrossRefPubMedCentralGoogle Scholar
  80. Savas HA, Gergerlioglu HS, Armutcu F, Herken H, Yilmaz HR, Kocoglu E, Selek S, Tutkun H, Zoroglu SS, Akyol O (2006) Elevated serum nitric oxide and superoxide dismutase in euthymic bipolar patients: impact of past episodes. World J Biol Psychiatry 7(1):51–55PubMedCrossRefPubMedCentralGoogle Scholar
  81. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird T, Hardy J, Hutton M, Kukull W, Larson E, Levy-Lahad L, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt SD, Younkin S (1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer’s disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer’s disease. Nat Med 2:864–870PubMedCrossRefPubMedCentralGoogle Scholar
  82. Schneider P, Hampel H, Buerger K (2009) Biological marker candidates of Alzheimer’s disease in blood, plasma, and serum. CNS Neurosci Ther 15:358–374PubMedCrossRefPubMedCentralGoogle Scholar
  83. Schupf N, Tang MX, Fukuyama H, Manly J, Andrews H, Mehta P, Ravetch J, Mayeux R (2008) Peripheral Abeta subspecies as risk biomarkers of Alzheimer’s disease. Proc Natl Acad Sci U S A 105:14052–14057PubMedPubMedCentralCrossRefGoogle Scholar
  84. Selek S, Savas HA, Gergerlioglu HS, Bulbul F, Uz E, Yumru M (2008) The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. J Affect Disord 107(1–3):89–94PubMedCrossRefPubMedCentralGoogle Scholar
  85. Sharma SK, Sood S, Sharma A, Gupta ID (2013) Estimation of serum zinc and copper levels patients with schizophrenia: a preliminary study. Sri Lanka J Psychiatry 5(1):14–17CrossRefGoogle Scholar
  86. Shekhar S, Kumar R, Rai N, Kumar V, Singh K, Upadhyay AD, Tripathi M, Dwivedi S, Dey AB, Dey S (2016) Estimation of tau and phosphorylated Tau181 in serum of Alzheimer’s disease and mild cognitive impairment patients. PLoS One 11(7):e0159099PubMedPubMedCentralCrossRefGoogle Scholar
  87. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003) α-Synuclein locus triplication causes Parkinson’s disease. Science 302(5646):841PubMedCrossRefPubMedCentralGoogle Scholar
  88. Siwek M, Styczén K, Sowa-Kućma M, Dudek D, Reczyński W, Szewczyk B, Misztak P, Opoka W, Topór-Mądry R, Nowak G, Rybakowski JK (2017) The serum concentration of copper in bipolar disorder. Psychiatr Pol 51:469–481PubMedCrossRefPubMedCentralGoogle Scholar
  89. Southwell AL, Smith EP, Davis TR, Caron NS, Villanueva EB, Xie Y, Collins JA, Ye ML, Sturrock A, Leavitt BR, Schrum AG, Hayden MR (2015) Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression. Sci Rep 5:12166PubMedPubMedCentralCrossRefGoogle Scholar
  90. 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(8):1153–1161PubMedCrossRefGoogle Scholar
  91. Squitti R, Polimanti R (2013) Copper phenotype in Alzheimer’s disease: dissecting the pathway. Am J Neurodegener Dis 2:46–56PubMedPubMedCentralGoogle Scholar
  92. Steinacker P, Hawlik A, Lehnert S, Jahn O, Meier S, Görz E, Braunstein KE, Krzovska M, Schwalenstöker B, Jesse S, Pröpper C, Böckers T, Ludolph A, Otto M (2010) Neuroprotective function of cellular prion protein in a mouse model of amyotrophic lateral sclerosis. Am J Pathol 176:1409–1420PubMedPubMedCentralCrossRefGoogle Scholar
  93. Subramanian KS (1996) Determination of metals in biofluids and tissues: sample preparation methods for atomic spectroscopic techniques. Spectrochim Acta B At Spectrosc 51(3):291–319CrossRefGoogle Scholar
  94. Sussulini A, Becker JS, Becker JS (2017) Laser ablation ICP-MS: application in biomedical research. Mass Spectrom Rev 36:47–57PubMedPubMedCentralCrossRefGoogle Scholar
  95. Sussulini A, Kratzin H, Jahn O, Banzato CE, Arruda MA, Becker JS (2010) Metallomics studies of human blood serum from treated bipolar disorder patients. Anal Chem 82(13):5859–5864PubMedCrossRefPubMedCentralGoogle Scholar
  96. Sussulini A, Matusch A, Klietz M, Bauer A, Depboylu C, Becker JS (2012) Quantitative imaging of Cu, Fe, Mn and Zn in the L-DOPA-treated unilateral 6-hydroxydopamine Parkinson’s disease mouse model by LA-ICP-MS. Biomed Spectrosc Imaging 1:125–136Google Scholar
  97. Tórsdóttir G, Kristinsson J, Sveinbjörnsdóttir S, Snaedal J, Jóhannesson T (1999) Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Pharmacol Toxicol 85(5):239–243PubMedCrossRefPubMedCentralGoogle Scholar
  98. Tyrer SP, Delves HT, Weller MP (1979) CSF copper in schizophrenia. Am J Psychiatry 136(7):937–939PubMedCrossRefPubMedCentralGoogle Scholar
  99. van Oijen M, Hofman A, Soares HD, Koudstaal PJ, Breteler MM (2006) Plasma Abeta(1-40) and Abeta(1-42) and the risk of dementia: a prospective case-cohort study. Lancet Neurol 5:655–660PubMedCrossRefPubMedCentralGoogle Scholar
  100. Ventriglia M, Bucossi S, Panetta V, Squitti R (2012) Copper in Alzheimer’s disease: a meta-analysis of serum, plasma, and cerebrospinal fluid studies. J Alzheimers Dis 30:981–984PubMedCrossRefPubMedCentralGoogle Scholar
  101. Virit O, Altindag A, Selek S, Yumru M, Bulut M, Erel O, Savas HA, Herken H (2008) Increased plasma ceruloplasmin levels in schizophrenia. Klinik Psikofarmakoloji Bülteni 18:282–287Google Scholar
  102. Wisnieff C, Ramanan S, Olesik J, Gauthier S, Wang Y, Pitt D (2015) Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: interpreting positive susceptibility and the presence of iron. Magn Reson Med 74:564–570PubMedCrossRefPubMedCentralGoogle Scholar
  103. Wu JQ, Kosten TR, Zhang XY (2013) Free radicals antioxidant defense systems, and schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 46:200–206CrossRefGoogle Scholar
  104. Yanik M, Kocyigit A, Tutkun H, Vural H, Herken H (2004) Plasma manganese, selenium, zinc, copper, and iron concentrations in patients with schizophrenia. Biol Trace Elem Res 98:109–117PubMedCrossRefPubMedCentralGoogle Scholar
  105. Zetterberg H, Wilson D, Andreasson U, Minthon L, Blennow K, Randall J, Hansson O (2013) Plasma tau levels in Alzheimer’s disease. Alzheimers Res Ther 5(2):9PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Bioanalytics and Integrated Omics (LaBIOmics), Department of Analytical Chemistry, Institute of ChemistryUniversity of Campinas (UNICAMP)CampinasBrazil
  2. 2.Spectrometry, Sample Preparation and Mechanization Group (GEPAM), Department of Analytical Chemistry, Institute of ChemistryUniversity of Campinas (UNICAMP)CampinasBrazil
  3. 3.National Institute of Science and Technology for Bioanalytics – INCTBio, Institute of Chemistry, University of Campinas (UNICAMP)CampinasBrazil
  4. 4.Centro de Estudos da Saúde do Trabalho e Ecologia Humana (CESTEH), Escola Nacional de Saúde Pública Sérgio Arouca (ENSP), FIOCRUZ, Rua Leopoldo BulhõesRio de JaneiroBrazil

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