Die Bedeutung des Coeruloplasmins für die Differenzialdiagnose neuropsychiatrischer Störungen

Zusammenfassung

Das psychiatrische Interesse am Coeruloplasmin geht ursprünglich auf Beobachtungen erhöhten Serumkupfers bei Schizophrenien zurück. Das immunturbidimetrisch bestimmte Serum-Coeruloplasmin ist jedoch, anscheinend im Gegensatz zur Coeruloplasmin-assoziierten Oxidaseaktivität, bei den Schizophrenien nicht erhöht. Da das Coeruloplasmin als Akut-Phase-Protein bei zahlreichen Prozessen ansteigt, ist eine erhöhte Coeruloplasmin-Serumkonzentration aus neuropsychiatrischer Sicht wenig aussagekräftig. Dagegen scheint die Coeruloplasmin-Oxidaseaktivität bei Morbus Alzheimer reduziert zu sein, und niedrige immunturbidimetrisch bestimmte Coeruloplasmin-Serumkonzentrationen oder ein Fehlen des Serum-Coeruloplasmins werden bei Morbus Wilson, Menkes Disease und Acoeruloplasminämie angetroffen, 3 erblichen neurodegenerativen Systemerkrankungen mit ausgeprägter genotypischer, vor allem aber auch phänotypischer Variabilität. Insbesondere Morbus Wilson kann über lange Zeiträume eine ausschließlich psychische Symptomatik zeigen. Heterozygote Merkmalsträger von Morbus Wilson und Acoeruloplasminämie zeigen niedrige Coeruloplasmin-Serumkonzentrationen ohne wesentliche weitere körperliche Befunde. Ob psychische Störungen auch bei den hiervon Betroffenen oder, allgemeiner, bei niedriger Coeruloplasmin-Serumkonzentration ohne manifesten Morbus Wilson gehäuft auftreten, wurde bisher nicht untersucht.

Abstract

The blue copper protein ceruloplasmin has been of interest to psychiatrists for decades following Heilmeyer’s observation of elevated serum copper levels in schizophrenic patients. Immunoturbidimetry, however, does not yield elevated serum ceruloplasmin concentrations in schizophrenia while ceruloplasmin-related oxidase activity appears to be elevated in patients with schizophrenia and reduced in patients with Alzheimer’s disease. Low serum concentrations of immunoturbidimetrically measured ceruloplasmin, and of oxidase activity, are typical of Wilson’s disease, Menkes’ disease, and aceruloplasminemia, three familial neurodegenerative disorders of pronounced variability, with regard to both genotype and phenotype. Especially patients with Wilson’s disease may exhibit behavioural symptoms only over a long period. Heterozygous carriers of Wilson’s disease and aceruloplasminaemia may have low serum ceruloplasmin concentrations; they will not develop somatic symptoms, but the significance of these carrier states, or of ”hypoceruloplasminaemia”, with regard to mental disorders is unknown.

Schlüsselwörter

Metallstoffwechsel - angeborene Stoffwechselstörungen - Hirnerkrankungen - heredodegenerative Störungen - neurologische und Verhaltensstörungen

Keywords

metal metabolism - inborn errors of metabolism - brain diseases - heredodegenerative disorders - neurobehavioural manifestations

Literatur

• 1 Abood L G, Gibbs F A, Gibbs E. Comparative study of blood ceruloplasmin in schizophrenia and other disorders.  AMA Arch Neurol Psychiatr. 1957;  77 643-645
• 2 Adams P C, Strand R D, Bresnan M J et al. Kinky hair syndrome: serial study of radiological findings with emphasis on the similarity to the battered child syndrome.  Radiology. 1974;  112 401-407
• 3 Affleck J W, Cooper A J, Forrest A D et al. Penicillamine and schizophrenia – a clinical trial.  Br J Psychiatry. 1969;  115 173-6
• 4 Ala A, Walker A P, Ashkan K et al. Wilson’s disease.  Lancet. 2007;  9559 397-408
• 5 Akerfeldt S. Oxidation of N, N-dimethyl-p-phenylenediamine by serum from patients with mental disease.  Science. 1957;  125 (3238) 117-119
• 6 Akil M, Brewer G J. Psychiatric and Behavioral Abnormalities in Wilson`s Disease.  Behav Neurol Movement Disorders. 1995;  65 171-178
• 7 Akil M, Schwartz J A, Dutchak D et al. The psychiatric presentations of Wilson`s disease.  J Neuropsychiatry. 1991;  3 377-382
• 8 Andrews G S. Studies of plasma zinc, copper, caeruloplasmin, and growth hormone: with special reference to carcinoma of the bronchus.  J Clin Pathol. 1979;  32 325-33
• 9 Armendariz A D, Gonzalez M, Alexander V et al. Gene expression profiling in chronic copper overload reveals upregulation of Prnp and App.  Physiol Genomics. 2004;  20 45-54
• 10 Atwood C S, Moir R D, Huang X et al. Dramatic aggregation of Alzheimer abeta by Cu[II] is induced by conditions representing physiological acidosis.  J Biol Chem. 1998;  273 12 817-12 826
• 11 Baerlocher K, Nadal D. Menkes syndrome.  Ergeb Inn Med Kinderheilkd. 1988;  57 77-144
• 12 Bammer H. Caeruloplasmin- und Kupferstoffwechsel bei Multipler Sklerose.  Dtsch Z Nervenheilkd. 1966;  189 312-329
• 13 Barceloux D G. Copper.  Clin Toxicol. 1999;  37 217-230
• 14 Bock E, Weeke B, Rafaelsen O J. Serum proteins in acutely psychotic patients.  J Psychiatr Res. 1971;  9 (1) 1-9
• 15 Bock E, Kristensen V, Rafaelsen O J. Proteins in serum and cerebrospinal fluid in demented patients.  Acta Neurol Scand. 1974;  50 91-102
• 16 Bowman M B, Lewis M S. The copper hypothesis of schizophrenia: a review.  Neurosci Biobehav Rev. 1982;  6 321-328
• 17 Brewer G J, Askari F, Lorincz M T et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease.  Arch Neurol. 2006;  63 521-527
• 18 Brewer G J, Askari F. Wilson’s disease: clinical management and therapy.  J Hepatol. 2005;  42 S13-S21
• 19 Brewer G J, Terry C A, Aisen A M et al. Worsening of neurologic syndrome in patients with Wilson’s disease with initial penicillamine therapy.  Arch Neurol. 1987;  44 490-493
• 20 Brewer G J. Behavioral abnormalities in Wilson’s disease.  Adv Neurol. 2005;  96 262-274
• 21 Brewer G J. Neurologically presenting Wilson’s disease: epidemiology, pathophysiology and treatment.  CNS Drugs. 2005;  19 185-192
• 22 Brooker B K, Papeschi R, Murray L. Negative results of a trial of penicillamine in chronic schizophrenia.  Postgrad Med J. 1968;  Suppl 48-55
• 23 Bull P C, Thomas G R, Rommens J M et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene.  Nat Genet. 1993;  5 327-335
• 24 Bux C J, Rosenbohm A, Connemann B J. Morbus Wilson als Differentialdiagnose bei psychischen Störungen.  Nervenheilkd. 2007;  26 150-155
• 25 Burrows S, Pekala B. Serum copper and ceruloplasmin in pregnancy.  Am J Obstet Gynecol. 1971;  109 907-909
• 26 Calabrese L, Carbonaro M, Musci G. Presence of coupled trinuclear copper cluster in mammalian ceruloplasmin is essential for efficient electron transfer to oxygen.  J Biol Chem. 1989;  264 6183-6187
• 27 Capo C R, Arciello M, Squitti R et al. Features of ceruloplasmin in the cerebrospinal fluid of Alzheimer’s disease patients.  Biometals. 2008;  21 367-372
• 28 Carruthers M E, Hobbs C B, Warren R L. Raised serum copper and caeruloplasmin levels in subjects taking oral contraceptives.  J Clin Pathol. 1966;  19 498-500
• 29 Castellani R J, Smith M A, Nunomura A et al. Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin?.  Free Radic Biol Med. 1999;  26 1508-1512
• 30 Cauza E, Maier-Dobersberger T, Polli C et al. Screening for Wilson’s disease in patients with liver diseases by serum ceruloplasmin.  J Hepatol. 1997;  27 358-362
• 31 Chan K H. Wilson’s disease with depression and parkinsonism.  J Clin Neurosci. 2005;  12 303-305
• 32 Church W R, Jernigan R L, Toole J et al. Coagulation factors V and VIII and ceruloplasmin constitute a family of structurally related proteins.  Proc Natl Acad Sci USA. 1984;  81 6934-6947
• 33 Connor J R, Tucker P, Johnson M et al. Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer’s disease.  Neurosci Lett. 1993;  159 88-90
• 34 Cox D W. Factors influencing serum ceruloplasmin levels in normal individuals.  J Lab Clin Med. 1966;  68 893-904
• 35 Cox D W, Roberts E A. Wilson Disease. [online]. GeneClinics, University of Washington. Seattle; 2006 http://www.geneclinics.org/profiles/wilson/details.html
• 36 Cumings J N. The copper and iron content of brain and liver in the normal and in hepatolenticular degeneration.  Brain. 1948;  71 410-415
• 37 Daimon M, Susa S, Yamatani K et al. Hyperglycemia is a factor for an increase in serum ceruloplasmin in type 2 diabetes.  Diabetes Care. 1998;  21 1525-1528
• 38 Daly W J, Rabinovitch H H. Urologic abnormalities in Menkes’ syndrome.  J Urol. 1981;  126 262-264
• 39 Danks D M, Campbell P E, Walker-Smith J et al. Menkes’ kinky-hair syndrome.  Lancet. 1972;  7760 1100-1102
• 40 Daunter B, Elstein M. Serum levels of copper, caeruloplasmin and caeruloplasmin oxidase activity in women using copper-containing intrauterine devices and in women taking combined oral contraceptives.  J Obstet Gynaecol Br Commonw. 1973;  80 644-647
• 41 Davidoff G N, Votaw M L, Coon W W et al. Elevations in serum copper, erythrocytic copper, and ceruloplasmin concentrations in smokers.  Am J Clin Pathol. 1978;  70 790-2
• 42 Dening T R, Berrios G E. Wilson`s disease: psychiatric symptoms in 195 cases.  Arch Gen Psychiatry. 1989;  46 1125-1134
• 43 Denny-Brown D, Porter H. The effect of BAL [2,3-dimercaptopropanol] on hepatolenticular degeneration (Wilson’s disease).  N Engl J Med. 1951;  245 917-925
• 44 Dumoulin M J, Chahine R, Atanasiu R et al. Comparative antioxidant and cardioprotective effects of ceruloplasmin, superoxide dismutase and albumin.  Arzneimittelforschung. 2006;  46 855-861
• 45 Engström G, Stavenow L, Hedblad B et al. Inflammation-sensitive plasma proteins and incidence of myocardial infarction in men with low cardiovascular risk.  Arterioscler Thromb Vasc Biol. 2003;  23 2247-2251
• 46 Farver O, Bendahl L, Skov L K et al. Human ceruloplasmin. Intramolecular electron transfer kinetics and equilibration.  J Biol Chem. 1999;  1274 26 135-26 140
• 47 Ferenci P. Pathophysiology and clinical features of Wilson’s disease.  Metab Brain Dis. 2004;  19 229-239
• 48 Ferenci P. Wilson’s Disease.  Clin Gastroenterol Hepatol. 2005;  3 726-733
• 49 Fleischer B. Über eine der ‘Pseudosklerose’ nahestehende bisher unbekannte Krankheit (gekennzeichnet durch Tremor, psychische Störung, bräunliche Pigmentierung bestimmter Gewebe, insbesondere auch der Hornhautperipherie, Lebercirrhose).  Deutsche Z Nervenheilkd (J Neurol). 1912;  44 179-201
• 50 Fleischer B. Zwei weitere Fälle von grünlicher Verfärbung der Kornea.  Klin Monatsbl Augenheilkd. 1903;  41 489-491
• 51 Frydman M, Bonne-Tamir B, Farrer L A et al. Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase D locus.  Proc Natl Acad Sci USA. 1985;  82 1819-1821
• 52 Gaffney D, Fell G S, O’Reilly D S. ACP Best Practice No 163. Wilson’s disease: acute and presymptomatic laboratory diagnosis and monitoring.  J Clin Pathol. 2000;  53 807-812
• 53 Ganrot P O. Variation of the concentrations of some plasma proteins in normal adults, in pregnant women and in newborns.  Scand J Clin Lab Invest Suppl. 1972;  124 83-88
• 54 Giometto B, Argentiero V, Sanson F et al. Acute-phase proteins in Alzheimer’s disease.  Eur Neurol. 1988;  28 30-33
• 55 Gitlin J D. Transcriptional regulation of ceruloplasmin gene expression during inflammation.  J Biol Chem. 1988;  263 6281-6287
• 56 Goldstein I M, Kaplan H B, Edelson H S. Ceruloplasmin. A scavenger of superoxide anion radicals.  J Biol Chem. 1979;  254 4040-4045
• 57 Greiner A C, Berry K. Skin pigmentation and corneal and lens opacities with prolonged chlorpromazine therapy.  Can Med Assoc J. 1964;  90 663-665
• 58 Greiner A C, Nicolson G A. New side effects in prolonged chlorpromazine therapy.  Can Psychiatr Assoc J. 1965;  10 109-111
• 59 Gutteridge J M. Inhibition of the Fenton reaction by the protein ceruloplasmin and other copper complexes. Assessment of feroxidase and radical scavenging activities.  Chem Biol Interact. 1985;  56 113-120
• 60 Harada M. Wilson disease.  Med Electron Microsc. 2002;  35 61-66
• 61 Harris Z L, Durley A P, Man T K et al. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux.  Proc Natl Acad Sci USA. 1999;  96 10 812-10 817
• 62 Harris Z L. Not All Absent Serum Ceruloplasmin Is Wilson Disease: A Review of Aceruloplasminemia.  J Investig Med. 2002;  50 236-238
• 63 Healy J, Tipton K. Ceruloplasmin and what it might do.  J Neural Transm. 2007;  114 777-781
• 64 Heilmeyer L, Keiderling W, Struve C. Kupfer und Eisen als körpereigne Wirkstoffe und ihre Bedeutung beim Krankheitsgeschehen. Jena: Fischer; 1941
• 65 Hellman N E, Gitlin J D. Ceruloplasmin metabolism and function.  Annu Rev Nutr. 2002;  22 439-458
• 66 Helmchen H, Hippius H, Hoffmann I et al. D-Penicillamin in der Schizophreniebehandlung.  Nervenarzt. 1967;  38 218-220
• 67 Hitoshi S, Iwata M, Yoshikawa K. Mid-brain pathology of Wilson’s disease: MRI analysis of three cases.  J Neurol Neurosurg Psychiatry. 1991;  54 624-626
• 68 Holmberg C G, Laurell C B. (1948a). Investigations in serum copper. II. Isolation of the copper-containing protein and a description of some of its properties.  Acta Chem Scand. 1948;  2 550-556
• 69 Holmberg C G, Laurell C B. (1948b). Histaminolytic activity of a copper protein in serum.  Nature. 1948;  161 (4085) 236
• 70 Holtzman N A, Gaumnitz B M. Studies on the rate of release and turnover of ceruloplasmin and apoceruloplasmin in rat plasma.  J Biol Chem. 1970;  245 2354-2358
• 71 Ichihara K, Kawai T. Determination of reference intervals for 13 plasma proteins based on IFCC international reference preparation [CRM470] and NCCLS proposed guideline [C28-P,1992]: trial to select reference individuals by results of screening tests and application of maximal likelihood method.  J Clin Lab Anal. 1996;  10 110-117
• 72 Jacobs D A, Markowitz C E, Liebeskind D S et al. The „double panda sign” in Wilson’s disease.  Neurology. 2003;  61 969
• 73 Jeandel C, Nicolas M B, Dubois F et al. Lipid peroxidation and free radical scavengers in Alzheimer’s disease.  Gerontology. 1989;  35 275-282
• 74 Jukic I et al. Psychosis and Wilson’s disease: a case report.  Psychiatr Danub. 2006;  18 105-107
• 75 Kaneko K, Yoshida K, Arima K et al. Astrocytic deformity and globular structures are characteristic of the brains of patients with aceruloplasminemia.  J Neuropathol Exp Neurol. 2002;  61 1069-1077
• 76 Kayser B. Über einen Fall von angeborener grünlicher Verfärbung der Cornea.  Klin Monatsbl Augenheilkd. 1902;  40 22-25
• 77 Kim R H, Park J E, Park J W. Ceruloplasmin enhances DNA damage induced by hydrogen peroxide in vitro.  Free Radical Res. 2000;  33 81-89
• 78 Klomp L W, Farhangrazi Z S, Dugan L L et al. Ceruloplasmin gene expression in the murine central nervous system.  J Clin Invest. 1996;  98 207-215
• 79 Klomp L W, Gitlin J D. Expression of the ceruloplasmin gene in the human retina and brain: implications for a pathogenic model in aceruloplasminemia.  Hum Mol Genet. 1996;  5 1989-1996
• 80 Kono S, Miyajima H. Molecular and pathological basis of aceruloplasminemia.  Biol Res. 2006;  39 15-23
• 81 Koschinsky M L, Funk W D, Oost B A et al. Complete cDNA sequence of human preceruloplasmin.  Proc Natl Acad Sci USA. 1986;  83 5086-5090
• 82 Kunath van B, Reuner U. Diagnostik und Therapie bei Morbus Wilson.  Akt Neurol. 2003;  30 18-26
• 83 Lehmann H P, Schosinsky K H, Beeler M F. Standardization of serum ceruloplasmin concentrations in international enzyme units with o-dianisidine dihydrochloride as substrate.  Clin Chem. 1974;  20 1564-1567
• 84 Loeffler D A, DeMaggio A J, Juneau P L et al. Ceruloplasmin is increased in cerebrospinal fluid in Alzheimer’s disease but not Parkinson’s disease.  Alzheimer Dis Assoc Disord. 1994;  8 190-197
• 85 Loeffler D A, LeWitt P A, Juneau P L et al. Increased regional brain concentrations of ceruloplasmin in neurodegenerative disorders.  Brain Res. 1996;  738 265-274
• 86 Lovell M A, Robertson J D, Teesdale W J et al. Copper, iron and zinc in Alzheimer’s disease senile plaques.  J Neurol Sci. 1998;  158 47-52
• 87 Mandelbrote B M, Stanier M W, Thompson R H et al. Studies on copper metabolism in demyelinating disease of the central nervous system.  Brain. 1948;  71 212
• 88 Markowitz H, Gubler C J, Mahoney J P et al. Studies on copper metabolism. XIV. Copper, ceruloplasmin and oxidase activity in sera of normal human subjects, pregnant women, and patients with infection, hepatolenticular degeneration, and the nephritic syndrome.  J Clin Invest. 1955;  34 1498-1508
• 89 Martens S, Valbo S, Melander B. Studies on the role of ceruloplasmin in schizophrenia.  Acta psych neurol scand. 1959;  34 (Suppl 136) 349-360
• 90 Masi M, Paolucci P, Vecchi V et al. La ceruloplasminemia nel bambino normale.  Minerva Pediatr. 1975;  27 1175-1181
• 91 Matarazzo E B. Psychiatric Features and Disturbance of Circadian Rhythm of Temperature, Pulse, and Blood Pressure in Wilson’s Disease.  J Neuropsychiatry Clin Neurosci. 2002;  14 335-339
• 92 Matsuda I, Pearson T, Holtzman N A. 1974. Determination of apoceruloplasmin by radioimmunoassay in nutritional copper deficiency, Menkes’ kinky hair syndrome, Wilson’s disease, and umbilical cord blood.  Pediatr Res. 1974;  8 821-824
• 93 Mattke D J, Adler M. Mode of action of D-penicillamine in chronic schizophrenia.  Dis Nerv Syst. 1971;  32 388-391
• 94 McNeill A, Pandolfo M, Kuhn J et al. The neurological presentation of ceruloplasmin gene mutations.  Eur Neurol. 2008;  60 200-205
• 95 Mendenhall H W. Effect of oral contraceptives on serum protein concentrations.  Am J Obstet Gynecol. 1970;  106 750-753
• 96 Menkes J H. Menkes disease and Wilson disease: two sides of the same copper coin. Part I: Menkes disease.  Eur J Paediatr Neurol. 1999;  3 147-158
• 97 Menkes J H. Menkes disease and Wilson disease: two sides of the same copper coin. Part II: Wilson disease.  Eur J Paediatr Neurol. 1999;  3 245-253
• 98 Menkes J H, Alter M, Steigleder G K et al. A sex- linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration.  Pediatrics. 1962;  29 764-779
• 99 Merle U, Schaefer M, Ferenci P et al. Clinical presentation, diagnosis and long-term outcome of Wilson disease – a cohort study.  Gut. 2007;  56 115-120
• 100 Merlo S G, Fernandez Martin F. Alteraciones de la ceruloplasmina y el cobre sericos en epilepticos.  J Neurol Sci. 1969;  8 555-561
• 101 Messerschmidt A, Huber R. The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships.  Eur J Biochem. 1990;  187 341-352
• 102 Meyer L A, Durley A P, Prohaska J R et al. Copper transport and metabolism are normal in aceruloplasminemic mice.  J Biol Chem. 2001;  276 36 857-36 861
• 103 Milne D B, Johnson P E. Assessment of copper status: effect of age and gender on reference ranges in healthy adults.  Clin Chem. 1993;  39 883-887
• 104 Misra R, Bhambal S A, Misra N P et al. Serum copper, ceruloplasmin & iron in ischaemic heart disease.  Indian Heart J. 1978;  30 339-344
• 105 Miyajima H, Nishimura Y, Mizoguchi K et al. Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration.  Neurology. 1987;  37 761-767
• 106 Miyajima H. Aceruloplasminemia, an iron metabolic disorder.  Neuropathology. 2003;  23 345-350
• 107 Morell A G, Windsor J, Sternlieb I. et al .Measurement of concentration of ceruloplasmin in serum by determination of its oxidase activity. Laboratory diagnosis of liver diseases.. St Louis: Greene; 1968: 193-195
• 108 Morita H, Ikeda S, Yamamoto K et al. Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family.  Ann Neurol. 1995;  37 646-656
• 109 Mouithys-Mickalad A, Deby C, Deby-Dupont G et al. An electron spin resonance [ESR] study on the mechanism of ascorbyl radical production by metal-binding proteins.  Biometals. 1998;  11 81-88
• 110 Mukhopadhyay C K, Attieh Z K, Fox P L. Role of ceruloplasmin in cellular iron uptake.  Science. 1998;  279 (5351) 714-717
• 111 Multhaup G, Schlicksupp A, Hesse L et al. The amyloid precursor protein of Alzheimer’s disease in the reduction of copper [II] to copper [I].  Science. 1996;  271 (5254) 1406-1409
• 112 Multhaup G, Hesse L, Borchardt T et al. Autoxidation of amyloid precursor protein and formation of reactive oxygen species.  Adv Exp Med Biol. 1999;  448 183-192
• 113 Nicolson G A, Greiner A C, McFarlane W J et al. Effect of penicillamine on schizophrenic patients.  Lancet. 1966;  7433 344-347
• 114 Olantunbosun D, Akindele M, Adadevoh B et al. Serum copper in schizophrenia in Nigerians.  Br J Psychiatry. 1975;  127 119-121
• 115 Ono S, Kurisaki H. An unusual neurological disorder with abnormal copper metabolism.  J Neurol. 1988;  235 397-399
• 116 Osaki S, Johnson D A, Frieden E. The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum.  J Biol Chem. 1966;  241 2746-2751
• 117 Padiglia A, Medda R, Lorrai A et al. Modulation of 6-hydroxydopamine oxidation by various proteins.  Biochem Pharmacol. 1997;  53 1065-1068
• 118 Paris I, Dagnino-Subiabre A, Marcelain K et al. Copper neurotoxicity is dependent on dopamine-mediated copper uptake and one-electron reduction of aminochrome in a rat substantia nigra neuronal cell line.  J Neurochem. 2001;  77 519-529
• 119 Park Y S, Suzuki K, Taniguchi N et al. Glutathione peroxidase-like activity of caeruloplasmin as an important lung antioxidant.  FEBS Lett. 1999;  17 (458) 133-136
• 120 Patel B N, Dunn R J, David S. Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain.  J Biol Chem. 2000;  275 4305-4310
• 121 Petrukhin K, Fischer S G, Pirastu M et al. Mapping, cloning and genetic characterization of the region containing the Wilson disease gene.  Nat Genet. 1993;  5 338-343
• 122 Plum C M, Hansen S E. Studies on variations in serum copper and serum copper oxidase activity, together with studies on the copper content of the cerebrospinal fluid, with particular reference to the variations in multiple sclerosis.  Acta Psychiatr Scand Suppl. 1960;  35 41-78
• 123 Pojerová A, Továrek J. Ceruloplasmin in early childhood.  Acta Paediatr. 1960;  49 113-120
• 124 Procopis P, Camakaris J, Danks D M. A mild form of Menkes steely hair syndrome.  J Pediatr. 1981;  98 97-99
• 125 Rahman B, Rahman M A, Hassan Z. Variation of copper and ceruloplasmin levels with liver function tests in schizophrenic patients.  Biomedicine. 1978;  29 238-241
• 126 Rathbun J K. Neuropsychological aspects of Wilson’s disease.  Int J Neurosci. 1996;  85 221-229
• 127 Reunanen A, Knekt P, Aaran R K. Serum ceruloplasmin level and the risk of myocardial infarction and stroke.  Am J Epidemiol. 1992;  136 1082-1090
• 128 Riordan S M, Williams R. The Wilson’s disease gene and phenotypic diversity.  J Hepatol. 2001;  34 165-171
• 129 Roberts E A, Schilsky M L. A Practice Guideline on Wilson Disease.  Hepatology. 2003;  37 1475-1491
• 130 Roux H, Aquaron R, Grangier R et al. Serum caeruloplasmin in rheumatology.  Ann Rheum Dis. 1970;  29 689-690
• 131 Salzer J L, Lovejoy L, Linder M C et al. Ran-2, a glial lineage marker, is a GPI-anchored form of ceruloplasmin.  J Neurosci Res. 1998;  54 147-157
• 132 Sarkar J, Seshadri V, Tripoulas N A et al. Role of ceruloplasmin in macrophage iron efflux during hypoxia.  J Biol Chem. 2003;  278 44 018-44 024
• 133 Sartoris D J, Luzzatti L, Weaver D D et al. Type IX Ehlers-Danlos syndrome. A new variant with pathognomonic radiographic features.  Radiology. 1984;  152 665-670
• 134 Sato M, Gitlin J D. Mechanisms of copper incorporation during the biosynthesis of human ceruloplasmin.  J Biol Chem. 1991;  266 5128-5134
• 135 Scheinberg I. Ceruloplasmin test for Wilson’s disease.  Pediatrics. 1963;  31 160-161
• 136 Scheinberg I H, Gitlin D. Deficiency of ceruloplasmin in patients with hepatolenticular degeneration [Wilson’s disease].  Science. 1952;  116 (3018) 484-485
• 137 Scheinberg I H, Morell A G, Harris R S et al. Concentration of ceruloplasmin in plasma of schizophrenic patients.  Science. 1957;  126 (3279) 925-926
• 138 Schosinsky K H, Lehmann H P, Beeler M F. Automated determination of serum ceruloplasmin activity with o-dianisidine dihydrochloride as substrate.  Clin Chem. 1975;  21 757-759
• 139 Schwartz M, Fuchs S, Polak H et al. Psychiatric manifestations in Wilson`s disease.  Harefuah. 1993;  124 75-77
• 140 Secchi G C, Petrella A, Lomanto B et al. Ceruloplasmin activity in liver diseases. Quantitative determination and electrophoretic characterization.  Enzym biol clin. 1967;  8 33-41
• 141 Smith M A, Nunomura A, Zhu X et al. Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease.  Antioxid Redox Signal. 2000;  2 413-420
• 142 Snaedal J, Kristinsson J, Gunnarsdóttir S et al. Copper, ceruloplasmin and superoxide dismutase in patients with Alzheimer’s disease. A case-control study.  Dement Geriatr Cogn Disord. 1998;  9 239-242
• 143 Squitti R, Barbati G, Rossi L et al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF b-amyloid, and h-tau.  Neurology. 2006;  67 76-82
• 144 Squitti R, Bressi F, Pasqualetti P et al. Longitudinal prognostic value of serum „free” copper in patients with Alzheimer disease.  Neurology. 2009;  72 50-55
• 145 Squitti R, Quattrocchi C C, Salustri C et al. Ceruloplasmin fragmentation is implicated in ‘free’ copper deregulation of Alzheimer’s disease.  Prion. 2008;  2 23-27
• 146 Squitti R, Salustri C. Agents complexing copper as a therapeutic strategy for the treatment of Alzheimer’s disease.  Curr Alzheimer Res. 2009;  6 476-487
• 147 Stiller P, Kassubek J, Schönfeldt-Lecuona C et al. Wilson’s disease in psychiatric patients.  Psychiatry Clin Neurosci. 2002;  56 649
• 148 Stoj C, Kosman D J. Cuprous oxidase activity of yeast Fet3 p and human ceruloplasmin: implication for function.  FEBS Lett. 2003;  554 422-426
• 149 Störiko K. Normal values for 23 different human plasma proteins determined by single radial immunodiffusion.  Blut. 1968;  16 200-208
• 150 Strümpell A. Ueber die Westphal’sche Pseudosklerose und über diffuse Hirnsklerose, insbesondere bei Kindern.  Deutsche Zeitschrift für Nervenheilkunde (J Neurol). 1898;  12 115-149
• 151 Sunderman F W, Nomoto S. Measurement of human serum ceruloplasmin by its p-phenylenediamine oxidase activity.  Clin Chemistry. 1970;  16 903-910
• 152 Takahashi N, Ortel T L, Putnam F W. Single-chain structure of human ceruloplasmin: the complete amino acid sequence of the whole molecule.  Proc Natl Acad Sci USA. 1984;  81 390-394
• 153 Tanzi R E, Petrukhin K, Chernov I et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene.  Nat Genet. 1993;  5 344-350
• 154 Thompson R H, Watson D. Serum copper levels in pregnancy and in pre-eclampsia.  J Clin Pathol. 1949;  2 193-196
• 155 Tønnesen T, Kleijer W J, Horn N. Incidence of Menkes disease.  Hum Genet. 1991;  86 408-410
• 156 Turay, Kiss J, Szórády I et al. Untersuchungen über die Caeruloplasminaktivität im Säuglings- und Kindesalter.  Monatsschr Kinderheilkd. 1963;  111 403-409
• 157 Vassiliev V, Harris Z L, Zatta P. Coeruloplasmin in neurodegenerative diseases.  Brain Res Brain Res Rev. 2005;  49 633-640
• 158 Vulpe C D, Packman S. Cellular copper transport.  Annu Rev Nutr. 1995;  15 293-322
• 159 Waggoner D J, Bartnikas T B, Gitlin J D. The role of copper in neurodegenerative disease.  Neurobiol Dis. 1999;  6 221-230
• 160 Walshe J M. Diagnostic significance of reduced serum caeruloplasmin concentration in neurological disease.  Mov Disord. 2005;  20 1658-1661
• 161 Weiss W A. Normalwerte spezifischer Serumproteine im Kindes- und Erwachsenenalter.  Klin Wochenschr. 1965;  43 273-277
• 162 Westman J A, Richardson D C, Rennert O M et al. Atypical Menkes steely hair disease.  Am J Med Genet. 1988;  30 853-858
• 163 Wheeler E M, Roberts P F. Menkes’ steely hair syndrome.  Arch Dis Child. 1976;  51 269-274
• 164 Willvonseder R, Goldstein N P, McCall J T et al. A hereditary disorder with dementia, spastic dysarthria, vertical eye movement paresis, gait disturbance, splenomegaly, and abnormal copper metabolism.  Neurology. 1973;  23 1039-1049
• 165 Wilson S AK. Progressive lenticular degeneration: a familial nervous system disease associated with cirrhosis of the liver.  Brain. 1912;  34 295-509
• 166 Wolf T L, Kotun J, Meador-Woodruff J H. Plasma copper, iron, ceruloplasmin and ferroxidase activity in schizophrenia.  Schizophr Res. 2006;  86 167-171
• 167 Yanik M, Kocyigit A, Tutkun H et al. Plasma manganese, selenium, zinc, copper, and iron concentrations in patients with schizophrenia.  Biol Trace Elem Res. 2004;  98 109-117
• 168 Young S N, Curzon G. A method for obtaining linear reciprocal plots with caeruloplasmin and its application in a study of the kinetic parameters of caeruloplasmin substrates.  Biochem J. 1972;  129 273-283
• 169 Yunice A A, Lindeman R D, Czerwinski A W et al. Influence of age and sex on serum copper and ceruloplasmin levels.  J Gerontol. 1974;  29 277-281
• 170 Zaitsev V N, Zaitseva I, Papiz M et al. An X-ray crystallographic study of the binding sites of the azide inhibitor and organic substrates to ceruloplasmin, a multi-copper oxidase in the plasma.  J Biol Inorg Chem. 1999;  4 579-587