Download PDF
Fortschr Neurol Psychiatr 2010; 78(10): 582-589
DOI: 10.1055/s-0029-1245540
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Die Bedeutung des Coeruloplasmins für die Differenzialdiagnose neuropsychiatrischer Störungen

The Role of Ceruloplasmin in the Differential Diagnosis of Neuropsychiatric DisordersB. J. Connemann1 , C. Schönfeldt-Lecuona1 , H.-J. Maxon1 , W. Kratzer2 , J. Kassubek3
  • 1Klinik für Psychiatrie und Psychotherapie III, Universitätsklinikum Ulm
  • 2Zentrum für Innere Medizin, I. Medizinische Klinik, Universitätsklinikum Ulm
  • 3Klinik für Neurologie, Universitätsklinikum Ulm, RKU
Further Information

Publication History

Publication Date:
01 September 2010 (online)

    Permissions and Reprints

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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 4 Ala A, Walker A P, Ashkan K et al. Wilson’s disease.  Lancet. 2007;  9559 397-408
    Google Scholar
  • 5 Akerfeldt S. Oxidation of N, N-dimethyl-p-phenylenediamine by serum from patients with mental disease.  Science. 1957;  125 (3238) 117-119
    Google Scholar
  • 6 Akil M, Brewer G J. Psychiatric and Behavioral Abnormalities in Wilson`s Disease.  Behav Neurol Movement Disorders. 1995;  65 171-178
    Google Scholar
  • 7 Akil M, Schwartz J A, Dutchak D et al. The psychiatric presentations of Wilson`s disease.  J Neuropsychiatry. 1991;  3 377-382
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 11 Baerlocher K, Nadal D. Menkes syndrome.  Ergeb Inn Med Kinderheilkd. 1988;  57 77-144
    Google Scholar
  • 12 Bammer H. Caeruloplasmin- und Kupferstoffwechsel bei Multipler Sklerose.  Dtsch Z Nervenheilkd. 1966;  189 312-329
    Google Scholar
  • 13 Barceloux D G. Copper.  Clin Toxicol. 1999;  37 217-230
    Google Scholar
  • 14 Bock E, Weeke B, Rafaelsen O J. Serum proteins in acutely psychotic patients.  J Psychiatr Res. 1971;  9 (1) 1-9
    Google Scholar
  • 15 Bock E, Kristensen V, Rafaelsen O J. Proteins in serum and cerebrospinal fluid in demented patients.  Acta Neurol Scand. 1974;  50 91-102
    Google Scholar
  • 16 Bowman M B, Lewis M S. The copper hypothesis of schizophrenia: a review.  Neurosci Biobehav Rev. 1982;  6 321-328
    Google Scholar
  • 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
    Google Scholar
  • 18 Brewer G J, Askari F. Wilson’s disease: clinical management and therapy.  J Hepatol. 2005;  42 S13-S21
    Google Scholar
  • 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
    Google Scholar
  • 20 Brewer G J. Behavioral abnormalities in Wilson’s disease.  Adv Neurol. 2005;  96 262-274
    Google Scholar
  • 21 Brewer G J. Neurologically presenting Wilson’s disease: epidemiology, pathophysiology and treatment.  CNS Drugs. 2005;  19 185-192
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 24 Bux C J, Rosenbohm A, Connemann B J. Morbus Wilson als Differentialdiagnose bei psychischen Störungen.  Nervenheilkd. 2007;  26 150-155
    Google Scholar
  • 25 Burrows S, Pekala B. Serum copper and ceruloplasmin in pregnancy.  Am J Obstet Gynecol. 1971;  109 907-909
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 31 Chan K H. Wilson’s disease with depression and parkinsonism.  J Clin Neurosci. 2005;  12 303-305
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 34 Cox D W. Factors influencing serum ceruloplasmin levels in normal individuals.  J Lab Clin Med. 1966;  68 893-904
    Google Scholar
  • 35 Cox D W, Roberts E A. Wilson Disease. [online]. GeneClinics, University of Washington. Seattle; 2006 http://www.geneclinics.org/profiles/wilson/details.html
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 38 Daly W J, Rabinovitch H H. Urologic abnormalities in Menkes’ syndrome.  J Urol. 1981;  126 262-264
    Google Scholar
  • 39 Danks D M, Campbell P E, Walker-Smith J et al. Menkes’ kinky-hair syndrome.  Lancet. 1972;  7760 1100-1102
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 42 Dening T R, Berrios G E. Wilson`s disease: psychiatric symptoms in 195 cases.  Arch Gen Psychiatry. 1989;  46 1125-1134
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 47 Ferenci P. Pathophysiology and clinical features of Wilson’s disease.  Metab Brain Dis. 2004;  19 229-239
    Google Scholar
  • 48 Ferenci P. Wilson’s Disease.  Clin Gastroenterol Hepatol. 2005;  3 726-733
    Google Scholar
  • 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
    Google Scholar
  • 50 Fleischer B. Zwei weitere Fälle von grünlicher Verfärbung der Kornea.  Klin Monatsbl Augenheilkd. 1903;  41 489-491
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 54 Giometto B, Argentiero V, Sanson F et al. Acute-phase proteins in Alzheimer’s disease.  Eur Neurol. 1988;  28 30-33
    Google Scholar
  • 55 Gitlin J D. Transcriptional regulation of ceruloplasmin gene expression during inflammation.  J Biol Chem. 1988;  263 6281-6287
    Google Scholar
  • 56 Goldstein I M, Kaplan H B, Edelson H S. Ceruloplasmin. A scavenger of superoxide anion radicals.  J Biol Chem. 1979;  254 4040-4045
    Google Scholar
  • 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
    Google Scholar
  • 58 Greiner A C, Nicolson G A. New side effects in prolonged chlorpromazine therapy.  Can Psychiatr Assoc J. 1965;  10 109-111
    Google Scholar
  • 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
    Google Scholar
  • 60 Harada M. Wilson disease.  Med Electron Microsc. 2002;  35 61-66
    Google Scholar
  • 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
    Google Scholar
  • 62 Harris Z L. Not All Absent Serum Ceruloplasmin Is Wilson Disease: A Review of Aceruloplasminemia.  J Investig Med. 2002;  50 236-238
    Google Scholar
  • 63 Healy J, Tipton K. Ceruloplasmin and what it might do.  J Neural Transm. 2007;  114 777-781
    Google Scholar
  • 64 Heilmeyer L, Keiderling W, Struve C. Kupfer und Eisen als körpereigne Wirkstoffe und ihre Bedeutung beim Krankheitsgeschehen. Jena: Fischer; 1941
    Google Scholar
  • 65 Hellman N E, Gitlin J D. Ceruloplasmin metabolism and function.  Annu Rev Nutr. 2002;  22 439-458
    Google Scholar
  • 66 Helmchen H, Hippius H, Hoffmann I et al. D-Penicillamin in der Schizophreniebehandlung.  Nervenarzt. 1967;  38 218-220
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 69 Holmberg C G, Laurell C B. (1948b). Histaminolytic activity of a copper protein in serum.  Nature. 1948;  161 (4085) 236
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 72 Jacobs D A, Markowitz C E, Liebeskind D S et al. The „double panda sign” in Wilson’s disease.  Neurology. 2003;  61 969
    Google Scholar
  • 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
    Google Scholar
  • 74 Jukic I et al. Psychosis and Wilson’s disease: a case report.  Psychiatr Danub. 2006;  18 105-107
    Google Scholar
  • 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
    Google Scholar
  • 76 Kayser B. Über einen Fall von angeborener grünlicher Verfärbung der Cornea.  Klin Monatsbl Augenheilkd. 1902;  40 22-25
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 80 Kono S, Miyajima H. Molecular and pathological basis of aceruloplasminemia.  Biol Res. 2006;  39 15-23
    Google Scholar
  • 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
    Google Scholar
  • 82 Kunath van B, Reuner U. Diagnostik und Therapie bei Morbus Wilson.  Akt Neurol. 2003;  30 18-26
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 90 Masi M, Paolucci P, Vecchi V et al. La ceruloplasminemia nel bambino normale.  Minerva Pediatr. 1975;  27 1175-1181
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 93 Mattke D J, Adler M. Mode of action of D-penicillamine in chronic schizophrenia.  Dis Nerv Syst. 1971;  32 388-391
    Google Scholar
  • 94 McNeill A, Pandolfo M, Kuhn J et al. The neurological presentation of ceruloplasmin gene mutations.  Eur Neurol. 2008;  60 200-205
    Google Scholar
  • 95 Mendenhall H W. Effect of oral contraceptives on serum protein concentrations.  Am J Obstet Gynecol. 1970;  106 750-753
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 100 Merlo S G, Fernandez Martin F. Alteraciones de la ceruloplasmina y el cobre sericos en epilepticos.  J Neurol Sci. 1969;  8 555-561
    Google Scholar
  • 101 Messerschmidt A, Huber R. The blue oxidases, ascorbate oxidase, laccase and ceruloplasmin. Modelling and structural relationships.  Eur J Biochem. 1990;  187 341-352
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 105 Miyajima H, Nishimura Y, Mizoguchi K et al. Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration.  Neurology. 1987;  37 761-767
    Google Scholar
  • 106 Miyajima H. Aceruloplasminemia, an iron metabolic disorder.  Neuropathology. 2003;  23 345-350
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 110 Mukhopadhyay C K, Attieh Z K, Fox P L. Role of ceruloplasmin in cellular iron uptake.  Science. 1998;  279 (5351) 714-717
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 113 Nicolson G A, Greiner A C, McFarlane W J et al. Effect of penicillamine on schizophrenic patients.  Lancet. 1966;  7433 344-347
    Google Scholar
  • 114 Olantunbosun D, Akindele M, Adadevoh B et al. Serum copper in schizophrenia in Nigerians.  Br J Psychiatry. 1975;  127 119-121
    Google Scholar
  • 115 Ono S, Kurisaki H. An unusual neurological disorder with abnormal copper metabolism.  J Neurol. 1988;  235 397-399
    Google Scholar
  • 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
    Google Scholar
  • 117 Padiglia A, Medda R, Lorrai A et al. Modulation of 6-hydroxydopamine oxidation by various proteins.  Biochem Pharmacol. 1997;  53 1065-1068
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 123 Pojerová A, Továrek J. Ceruloplasmin in early childhood.  Acta Paediatr. 1960;  49 113-120
    Google Scholar
  • 124 Procopis P, Camakaris J, Danks D M. A mild form of Menkes steely hair syndrome.  J Pediatr. 1981;  98 97-99
    Google Scholar
  • 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
    Google Scholar
  • 126 Rathbun J K. Neuropsychological aspects of Wilson’s disease.  Int J Neurosci. 1996;  85 221-229
    Google Scholar
  • 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
    Google Scholar
  • 128 Riordan S M, Williams R. The Wilson’s disease gene and phenotypic diversity.  J Hepatol. 2001;  34 165-171
    Google Scholar
  • 129 Roberts E A, Schilsky M L. A Practice Guideline on Wilson Disease.  Hepatology. 2003;  37 1475-1491
    Google Scholar
  • 130 Roux H, Aquaron R, Grangier R et al. Serum caeruloplasmin in rheumatology.  Ann Rheum Dis. 1970;  29 689-690
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 134 Sato M, Gitlin J D. Mechanisms of copper incorporation during the biosynthesis of human ceruloplasmin.  J Biol Chem. 1991;  266 5128-5134
    Google Scholar
  • 135 Scheinberg I. Ceruloplasmin test for Wilson’s disease.  Pediatrics. 1963;  31 160-161
    Google Scholar
  • 136 Scheinberg I H, Gitlin D. Deficiency of ceruloplasmin in patients with hepatolenticular degeneration [Wilson’s disease].  Science. 1952;  116 (3018) 484-485
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 139 Schwartz M, Fuchs S, Polak H et al. Psychiatric manifestations in Wilson`s disease.  Harefuah. 1993;  124 75-77
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 147 Stiller P, Kassubek J, Schönfeldt-Lecuona C et al. Wilson’s disease in psychiatric patients.  Psychiatry Clin Neurosci. 2002;  56 649
    Google Scholar
  • 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
    Google Scholar
  • 149 Störiko K. Normal values for 23 different human plasma proteins determined by single radial immunodiffusion.  Blut. 1968;  16 200-208
    Google Scholar
  • 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
    Google Scholar
  • 151 Sunderman F W, Nomoto S. Measurement of human serum ceruloplasmin by its p-phenylenediamine oxidase activity.  Clin Chemistry. 1970;  16 903-910
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 154 Thompson R H, Watson D. Serum copper levels in pregnancy and in pre-eclampsia.  J Clin Pathol. 1949;  2 193-196
    Google Scholar
  • 155 Tønnesen T, Kleijer W J, Horn N. Incidence of Menkes disease.  Hum Genet. 1991;  86 408-410
    Google Scholar
  • 156 Turay, Kiss J, Szórády I et al. Untersuchungen über die Caeruloplasminaktivität im Säuglings- und Kindesalter.  Monatsschr Kinderheilkd. 1963;  111 403-409
    Google Scholar
  • 157 Vassiliev V, Harris Z L, Zatta P. Coeruloplasmin in neurodegenerative diseases.  Brain Res Brain Res Rev. 2005;  49 633-640
    Google Scholar
  • 158 Vulpe C D, Packman S. Cellular copper transport.  Annu Rev Nutr. 1995;  15 293-322
    Google Scholar
  • 159 Waggoner D J, Bartnikas T B, Gitlin J D. The role of copper in neurodegenerative disease.  Neurobiol Dis. 1999;  6 221-230
    Google Scholar
  • 160 Walshe J M. Diagnostic significance of reduced serum caeruloplasmin concentration in neurological disease.  Mov Disord. 2005;  20 1658-1661
    Google Scholar
  • 161 Weiss W A. Normalwerte spezifischer Serumproteine im Kindes- und Erwachsenenalter.  Klin Wochenschr. 1965;  43 273-277
    Google Scholar
  • 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
    Google Scholar
  • 163 Wheeler E M, Roberts P F. Menkes’ steely hair syndrome.  Arch Dis Child. 1976;  51 269-274
    Google Scholar
  • 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
    Google Scholar
  • 165 Wilson S AK. Progressive lenticular degeneration: a familial nervous system disease associated with cirrhosis of the liver.  Brain. 1912;  34 295-509
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar

PD Dr. Bernhard J. Connemann

Klinik für Psychiatrie und Psychotherapie III, Universitätsklinikum Ulm

Leimgrubenweg 12

89075 Ulm

Email: bernhard.connemann@uni-ulm.de

      >