Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Non-Ceruloplasmin Copper as a Stratification Biomarker of Alzheimer’s Disease Patients: How to Measure and Use It

Author(s): Rosanna Squitti*, Mariacarla Ventriglia, Alberto Granzotto, Stefano L. Sensi and Mauro Ciro A. Rongioletti

Volume 18, Issue 7, 2021

Published on: 21 October, 2021

Page: [533 - 545] Pages: 13

DOI: 10.2174/1567205018666211022085755

Price: $65

Abstract

Alzheimer’s Disease (AD) is a type of dementia very common in the elderly. A growing body of recent evidence has linked AD pathogenesis to Copper (Cu) dysmetabolism in the body. In fact, a subset of patients affected either by AD or by its prodromal form known as Mild Cognitive Impairment (MCI) have been observed to be unable to maintain a proper balance of Cu metabolism and distribution and are characterized by the presence in their serum of increased levels of Cu not bound to ceruloplasmin (non-ceruloplasmin Cu). Since serum non-ceruloplasmin Cu is a biomarker of Wilson's Disease (WD), a well-known condition of Cu-driven toxicosis, in this review, we propose that in close analogy with WD, the assessment of non-ceruloplasmin Cu levels can be exploited as a cost-effective stratification and susceptibility/risk biomarker for the identification of some AD/MCI individuals. The approach can also be used as an eligibility criterion for clinical trials aiming at investigating Cu-related interventions against AD/MCI.

Keywords: Alzheimer's disease, copper, non-ceruloplasmin copper, ceruloplasmin, zinc, biomarker, stratification, risk/susceptibility.

Next »
[1]
Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science 1992; 256(5054): 184-5.
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[2]
Masters CL, Selkoe DJ. Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2(6): a006262.
[http://dx.doi.org/10.1101/cshperspect.a006262] [PMID: 22675658]
[3]
Lahiri DK. There is no failure, only discovery-the year ahead for carving new paths. Curr Alzheimer Res 2020; 17(1): 1-2.
[http://dx.doi.org/10.2174/156720501701200320143813] [PMID: 32209035]
[4]
Sensi SL, Granzotto A, Siotto M, Squitti R. Copper and zinc dysregulation in Alzheimer’s disease. Trends Pharmacol Sci 2018; 39(12): 1049-63.
[http://dx.doi.org/10.1016/j.tips.2018.10.001] [PMID: 30352697]
[5]
Herrup K. The case for rejecting the amyloid cascade hypothesis. Nat Neurosci 2015; 18(6): 794-9.
[http://dx.doi.org/10.1038/nn.4017] [PMID: 26007212]
[6]
Morante S. The role of metals in beta-amyloid peptide aggregation: X-Ray spectroscopy and numerical simulations. Curr Alzheimer Res 2008; 5(6): 508-24.
[http://dx.doi.org/10.2174/156720508786898505] [PMID: 19075577]
[7]
Becaria A, Lahiri DK, Bondy SC, et al. Aluminum and copper in drinking water enhance inflammatory or oxidative events specifically in the brain. J Neuroimmunol 2006; 176(1-2): 16-23.
[http://dx.doi.org/10.1016/j.jneuroim.2006.03.025] [PMID: 16697052]
[8]
Lahiri DK, Maloney B. The “learn” (latent early-life associated regulation) model integrates environmental risk factors and the developmental basis of Alzheimer’s disease, and proposes remedial steps. Exp Gerontol 2010; 45(4): 291-6.
[http://dx.doi.org/10.1016/j.exger.2010.01.001] [PMID: 20064601]
[9]
Lahiri DK, Maloney B, Zawia NH. The LEARn model: an epigenetic explanation for idiopathic neurobiological diseases. Mol Psychiatry 2009; 14(11): 992-1003.
[http://dx.doi.org/10.1038/mp.2009.82] [PMID: 19851280]
[10]
Siotto M, Squitti R. Copper imbalance in Alzheimer’s disease: Overview of the exchangeable copper component in plasma and the intriguing role albumin plays. Coord Chem Rev 2018; 371: 86-95.
[http://dx.doi.org/10.1016/j.ccr.2018.05.020]
[11]
Bucossi S, Ventriglia M, Panetta V, et al. Copper in Alzheimer’s disease: a meta-analysis of serum,plasma, and cerebrospinal fluid studies. J Alzheimers Dis 2011; 24(1): 175-85.
[http://dx.doi.org/10.3233/JAD-2010-101473] [PMID: 21187586]
[12]
Li D-D, Zhang W, Wang Z-Y, Zhao P. Serum copper, zinc, and iron levels in patients with Alzheimer’s disease: A meta-analysis of case-control studies. Front Aging Neurosci 2017; 9(300): 300.
[http://dx.doi.org/10.3389/fnagi.2017.00300] [PMID: 28966592]
[13]
Schrag M, Mueller C, Oyoyo U, Smith MA, Kirsch WM. Iron, zinc and copper in the Alzheimer’s disease brain: a quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion. Prog Neurobiol 2011; 94(3): 296-306.
[http://dx.doi.org/10.1016/j.pneurobio.2011.05.001] [PMID: 21600264]
[14]
Squitti R, Simonelli I, Ventriglia M, et al. Meta-analysis of serum non-ceruloplasmin copper in Alzheimer’s disease. J Alzheimers Dis 2014; 38(4): 809-22.
[http://dx.doi.org/10.3233/JAD-131247] [PMID: 24072069]
[15]
Wang ZX, Tan L, Wang HF, et al. Serum iron, zinc, and copper levels in patients with Alzheimer’s disease: A replication study and meta-analyses. J Alzheimers Dis 2015; 47(3): 565-81.
[http://dx.doi.org/10.3233/JAD-143108] [PMID: 26401693]
[16]
Bucossi S, Mariani S, Ventriglia M, et al. Association between the c. 2495 A>G ATP7B Polymorphism and Sporadic Alzheimer’s Disease. Int J Alzheimers Dis 2011; 2011: 973692.
[http://dx.doi.org/10.4061/2011/973692] [PMID: 21760992]
[17]
Bucossi S, Polimanti R, Mariani S, et al. Association of K832R and R952K SNPs of Wilson’s disease gene with Alzheimer’s disease. J Alzheimers Dis 2012; 29(4): 913-9.
[http://dx.doi.org/10.3233/JAD-2012-111997] [PMID: 22356903]
[18]
Bucossi S, Polimanti R, Ventriglia M, et al. Intronic rs2147363 variant in ATP7B transcription factor-binding site associated with Alzheimer’s disease. J Alzheimers Dis 2013; 37(2): 453-9.
[http://dx.doi.org/10.3233/JAD-130431] [PMID: 23948886]
[19]
Liu HP, Lin WY, Wang WF, et al. Genetic variability in copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with Alzheimer’s disease in a Chinese population. J Biol Regul Homeost Agents 2013; 27(2): 319-27.
[PMID: 23830383]
[20]
McCann CJ, Jayakanthan S, Siotto M, et al. Single nucleotide polymorphisms in the human ATP7B gene modify the properties of the ATP7B protein. Metallomics 2019; 11(6): 1128-39.
[http://dx.doi.org/10.1039/C9MT00057G] [PMID: 31070637]
[21]
Mercer SW, Wang J, Burke R. In vivo modeling of the pathogenic effect of copper transporter mutations that cause menkes and Wilson diseases, motor neuropathy, and susceptibility to Alzheimer’s disease. J Biol Chem 2017; 292(10): 4113-22.
[http://dx.doi.org/10.1074/jbc.M116.756163] [PMID: 28119449]
[22]
Squitti R, Polimanti R, Bucossi S, et al. Linkage disequilibrium and haplotype analysis of the ATP7B gene in Alzheimer’s disease. Rejuvenation Res 2013; 16(1): 3-10.
[http://dx.doi.org/10.1089/rej.2012.1357] [PMID: 22950421]
[23]
Kepp KP, Squitti R. Copper imbalance in Alzheimer’s disease: Convergence of the chemistry and the clinic. Coord Chem Rev 2019; 397: 168-87.
[http://dx.doi.org/10.1016/j.ccr.2019.06.018]
[24]
Bellingham SA, Lahiri DK, Maloney B, La Fontaine S, Multhaup G, Camakaris J. Copper depletion down-regulates expression of the Alzheimer’s disease amyloid-beta precursor protein gene. J Biol Chem 2004; 279(19): 20378-86.
[http://dx.doi.org/10.1074/jbc.M400805200] [PMID: 14985339]
[25]
Huang X, Atwood CS, Hartshorn MA, et al. The A beta peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 1999; 38(24): 7609-16.
[http://dx.doi.org/10.1021/bi990438f] [PMID: 10386999]
[26]
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): 1406-9.
[http://dx.doi.org/10.1126/science.271.5254.1406] [PMID: 8596911]
[27]
Atwood CS, Scarpa RC, Huang X, et al. Characterization of copper interactions with alzheimer amyloid beta peptides: identification of an attomolar-affinity copper binding site on amyloid beta1-42. J Neurochem 2000; 75(3): 1219-33.
[http://dx.doi.org/10.1046/j.1471-4159.2000.0751219.x] [PMID: 10936205]
[28]
Cherny RA, Atwood CS, Xilinas ME, et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 2001; 30(3): 665-76.
[http://dx.doi.org/10.1016/S0896-6273(01)00317-8] [PMID: 11430801]
[29]
Cherny RA, Legg JT, McLean CA, et al. Aqueous dissolution of Alzheimer’s disease Abeta amyloid deposits by biometal depletion. J Biol Chem 1999; 274(33): 23223-8.
[http://dx.doi.org/10.1074/jbc.274.33.23223] [PMID: 10438495]
[30]
Huang X, Cuajungco MP, Atwood CS, et al. Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 1999; 274(52): 37111-6.
[http://dx.doi.org/10.1074/jbc.274.52.37111] [PMID: 10601271]
[31]
White AR, Multhaup G, Maher F, et al. The Alzheimer’s disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures. J Neurosci 1999; 19(21): 9170-9.
[http://dx.doi.org/10.1523/JNEUROSCI.19-21-09170.1999] [PMID: 10531420]
[32]
Bagheri S, Squitti R, Haertlé T, Siotto M, Saboury AA. Role of copper in the onset of Alzheimer’s disease compared to other metals. Front Aging Neurosci 2018; 9: 446.
[http://dx.doi.org/10.3389/fnagi.2017.00446] [PMID: 29472855]
[33]
Kim AC, Lim S, Kim YK. Metal ion effects on Aβ and Tau aggregation. Int J Mol Sci 2018; 19(1): E128.
[http://dx.doi.org/10.3390/ijms19010128] [PMID: 29301328]
[34]
Hoogenraad T. Wilson disease. 2001.
[35]
Członkowska A, Litwin T, Dusek P, et al. Wilson disease. Nat Rev Dis Primers 2018; 4(1): 21.
[http://dx.doi.org/10.1038/s41572-018-0018-3] [PMID: 30190489]
[36]
European Association for Study of Liver. Wilson’s disease. J Hepatol 2012; 56(3): 671-85.
[PMID: 22340672]
[37]
Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson disease: an update. Hepatology 2008; 47(6): 2089-111.
[http://dx.doi.org/10.1002/hep.22261] [PMID: 18506894]
[38]
Walshe JM. Wilson’s disease: the importance of measuring serum caeruloplasmin non-immunologically. Ann Clin Biochem 2003; 40(Pt 2): 115-21.
[http://dx.doi.org/10.1258/000456303763046021] [PMID: 12662398]
[39]
Litwin T, Gromadzka G, Szpak GM, Jabłonka-Salach K, Bulska E, Członkowska A. Brain metal accumulation in Wilson’s disease. J Neurol Sci 2013; 329(1-2): 55-8.
[http://dx.doi.org/10.1016/j.jns.2013.03.021] [PMID: 23597670]
[40]
Walshe JM, Gibbs KR. Brain copper in Wilson’s disease. Lancet 1987; 2(8566): 1030.
[http://dx.doi.org/10.1016/S0140-6736(87)92598-0] [PMID: 2889941]
[41]
Gitlin JD. Wilson disease. Gastroenterology 2003; 125(6): 1868-77.
[http://dx.doi.org/10.1053/j.gastro.2003.05.010] [PMID: 14724838]
[42]
Gouider-Khouja N. Wilson’s disease. Parkinsonism Relat Disord 2009; 15(Suppl. 3): S126-9.
[http://dx.doi.org/10.1016/S1353-8020(09)70798-9] [PMID: 20082972]
[43]
Fujiwara N, Iso H, Kitanaka N, et al. Effects of copper metabolism on neurological functions in Wistar and Wilson’s disease model rats. Biochem Biophys Res Commun 2006; 349(3): 1079-86.
[http://dx.doi.org/10.1016/j.bbrc.2006.08.139] [PMID: 16970921]
[44]
Reed E, Lutsenko S, Bandmann O. Animal models of Wilson disease. J Neurochem 2018; 146(4): 356-73.
[http://dx.doi.org/10.1111/jnc.14323] [PMID: 29473169]
[45]
James SA, Volitakis I, Adlard PA, et al. Elevated labile Cu is associated with oxidative pathology in Alzheimer disease. Free Radic Biol Med 2012; 52(2): 298-302.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.446] [PMID: 22080049]
[46]
Squitti R, Ghidoni R, Simonelli I, et al. Copper dyshomeostasis in Wilson disease and Alzheimer’s disease as shown by serum and urine copper indicators. J Trace Elem Med Biol 2018; 45: 181-8.
[http://dx.doi.org/10.1016/j.jtemb.2017.11.005] [PMID: 29173477]
[47]
Amtage F, Birnbaum D, Reinhard T, et al. Estrogen intake and copper depositions: implications for Alzheimer’s disease? Case Rep Neurol 2014; 6(2): 181-7.
[http://dx.doi.org/10.1159/000363688] [PMID: 25076894]
[48]
Squitti R, Simonelli I, Cassetta E, et al. Patients with increased non-ceruloplasmin copper appear a distinct sub-group of Alzheimer’s disease: A neuroimaging study. Curr Alzheimer Res 2017; 14(12): 1318-26.
[http://dx.doi.org/10.2174/1567205014666170623125156] [PMID: 28669331]
[49]
Squitti R, Siotto M, Cassetta E, El Idrissi IG, Colabufo NA. Measurements of serum non-ceruloplasmin copper by a direct fluorescent method specific to Cu(II). Clin Chem Lab Med 2017; 55(9): 1360-7.
[http://dx.doi.org/10.1515/cclm-2016-0843] [PMID: 28076308]
[50]
Squitti R, Ventriglia M, Gennarelli M, et al. Non-ceruloplasmin copper distincts subtypes in Alzheimer’s disease: a genetic study of ATP7B frequency. Mol Neurobiol 2017; 54(1): 671-81.
[http://dx.doi.org/10.1007/s12035-015-9664-6] [PMID: 26758278]
[51]
Tecchio F, Vecchio F, Ventriglia M, et al. Non-ceruloplasmin copper distinguishes A distinct subtype of Alzheimer’s disease: A study of EEG-derived brain activity. Curr Alzheimer Res 2016; 13(12): 1374-84.
[http://dx.doi.org/10.2174/1567205013666160603001131] [PMID: 27335037]
[52]
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12(3): 189-98.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[53]
Squitti R, Bressi F, Pasqualetti P, et al. Longitudinal prognostic value of serum “free” copper in patients with Alzheimer disease. Neurology 2009; 72(1): 50-5.
[http://dx.doi.org/10.1212/01.wnl.0000338568.28960.3f] [PMID: 19122030]
[54]
Squitti R, Ghidoni R, Siotto M, et al. Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease. Ann Neurol 2014; 75(4): 574-80.
[http://dx.doi.org/10.1002/ana.24136] [PMID: 24623259]
[55]
Siotto M, Simonelli I, Pasqualetti P, et al. Association between serum ceruloplasmin specific activity and risk of Alzheimer’s disease. J Alzheimers Dis 2016; 50(4): 1181-9.
[http://dx.doi.org/10.3233/JAD-150611] [PMID: 26836154]
[56]
Squitti R, Polimanti R, Siotto M, et al. ATP7B variants as modulators of copper dyshomeostasis in Alzheimer’s disease. Neuromolecular Med 2013; 15(3): 515-22.
[http://dx.doi.org/10.1007/s12017-013-8237-y] [PMID: 23760784]
[57]
Stremmel W, Meyerrose KW, Niederau C, Hefter H, Kreuzpaintner G, Strohmeyer G. Wilson disease: clinical presentation, treatment, and survival. Ann Intern Med 1991; 115(9): 720-6.
[http://dx.doi.org/10.7326/0003-4819-115-9-720] [PMID: 1929042]
[58]
Lai M, Wang D, Lin Z, Zhang Y. Small molecule copper and its relative metabolites in serum of cerebral ischemic stroke patients. J Stroke Cerebrovasc Dis 2016; 25(1): 214-9.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.09.020] [PMID: 26573522]
[59]
Squitti R, Mendez AJ, Simonelli I, Ricordi C. Diabetes and Alzheimer’s disease: Can elevated free copper predict the risk of the disease? J Alzheimers Dis 2017; 56(3): 1055-64.
[http://dx.doi.org/10.3233/JAD-161033] [PMID: 27983558]
[60]
Lauwens S, Costas-Rodríguez M, Delanghe J, Van Vlierberghe H, Vanhaecke F. Quantification and isotopic analysis of bulk and of exchangeable and ultrafiltrable serum copper in healthy and alcoholic cirrhosis subjects. Talanta 2018; 189: 332-8.
[http://dx.doi.org/10.1016/j.talanta.2018.07.011] [PMID: 30086927]
[61]
McMillin GA, Travis JJ, Hunt JW. Direct measurement of free copper in serum or plasma ultrafiltrate. Am J Clin Pathol 2009; 131(2): 160-5.
[http://dx.doi.org/10.1309/AJCP7Z9KBFINVGYF] [PMID: 19141375]
[62]
Squitti R, Negrouk V, Perera M, et al. Serum copper profile in patients with type 1 diabetes in comparison to other metals. J Trace Elem Med Biol 2019; 56: 156-61.
[http://dx.doi.org/10.1016/j.jtemb.2019.08.011] [PMID: 31472477]
[63]
Squitti R, Fostinelli S, Siotto M, et al. Serum copper is not altered in frontotemporal lobar degeneration. J Alzheimers Dis 2018; 63(4): 1427-32.
[http://dx.doi.org/10.3233/JAD-171074] [PMID: 29843237]
[64]
Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 2014; 13(6): 614-29.
[http://dx.doi.org/10.1016/S1474-4422(14)70090-0] [PMID: 24849862]
[65]
Congdon EE, Sigurdsson EM. Tau-targeting therapies for Alzheimer disease. Nat Rev Neurol 2018; 14(7): 399-415.
[http://dx.doi.org/10.1038/s41582-018-0013-z] [PMID: 29895964]
[66]
Sensi SL. Alzheimer’s disease, time to turn the tide. Aging (Albany NY) 2018; 10(10): 2537-8.
[http://dx.doi.org/10.18632/aging.101581] [PMID: 30317224]
[67]
Kepp KP. Ten challenges of the amyloid hypothesis of Alzheimer’s disease. J Alzheimers Dis 2017; 55(2): 447-57.
[http://dx.doi.org/10.3233/JAD-160550] [PMID: 27662304]
[68]
Alzforum. exposure, exposure, exposure? At CTAD, aducanumab scientists make a case | ALZFORUM. 2020. Availalble from: https://www.alzforum.org/news/conference-coverage/exposure-exposure-exposure-ctad-aducanumab-sci [Accessed on 04 May 2020
[69]
Jain KK. Role of biomarkers in personalized medicine. In: Textbook of personalized medicine. New York, NY: Humana Press 2015.
[http://dx.doi.org/10.1007/978-1-4939-2553-7_3]
[70]
Barnard ND, Bush AI, Ceccarelli A, et al. Dietary and lifestyle guidelines for the prevention of Alzheimer’s disease. Neurobiol Aging 2014; 35(Suppl. 2): S74-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.03.033] [PMID: 24913896]
[71]
Squitti R, Siotto M, Polimanti R. Low-copper diet as a preventive strategy for Alzheimer’s disease. Neurobiol Aging 2014; 35(Suppl. 2): S40-50.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.02.031] [PMID: 24913894]
[72]
Squitti R, Barbati G, Rossi L, et al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid, and h-tau. Neurology 2006; 67(1): 76-82.
[http://dx.doi.org/10.1212/01.wnl.0000223343.82809.cf] [PMID: 16832081]
[73]
Coelho FC, Squitti R, Ventriglia M, et al. Agricultural use of copper and its link to Alzheimer’s disease. Biomolecules 2020; 10(6): E897.
[http://dx.doi.org/10.3390/biom10060897] [PMID: 32545484]
[74]
Adlard PA, Bush AI. Metals and Alzheimer’s disease: How far have we come in the clinic? J Alzheimers Dis 2018; 62(3): 1369-79.
[http://dx.doi.org/10.3233/JAD-170662] [PMID: 29562528]
[75]
Gella A, Solé M, Bolea I, et al. A comparison between radiometric and fluorimetric methods for measuring SSAO activity. J Neural Transm (Vienna) 2013; 120(6): 1015-8.
[http://dx.doi.org/10.1007/s00702-013-0987-z] [PMID: 23400361]
[76]
Unzeta M, Solé M, Boada M, Hernández M. Semicarbazide-sensitive amine oxidase (SSAO) and its possible contribution to vascular damage in Alzheimer’s disease. J Neural Transm (Vienna) 2007; 114(6): 857-62.
[http://dx.doi.org/10.1007/s00702-007-0701-0] [PMID: 17393059]
[77]
El Balkhi S, Trocello JM, Poupon J, et al. Relative exchangeable copper: a new highly sensitive and highly specific biomarker for Wilson’s disease diagnosis. Clin Chim Acta 2011; 412(23-24): 2254-60.
[http://dx.doi.org/10.1016/j.cca.2011.08.019] [PMID: 21878323]
[78]
Squitti R, Ghidoni R, Scrascia F, et al. Free copper distinguishes mild cognitive impairment subjects from healthy elderly individuals. J Alzheimers Dis 2011; 23(2): 239-48.
[http://dx.doi.org/10.3233/JAD-2010-101098] [PMID: 20930297]
[79]
Squitti R, Pasqualetti P, Polimanti R, et al. Metal-score as a potential non-invasive diagnostic test for Alzheimer’s disease. Curr Alzheimer Res 2013; 10(2): 191-8.
[http://dx.doi.org/10.2174/1567205011310020009] [PMID: 23036026]
[80]
Sperling M. Atomic absorption spectrometry. Weinheim: Wiley-VCH 1999.
[81]
Jarvis K, Gray A, Houk R. Inductively coupled plasma mass spectrometry. Blackie 1992.
[http://dx.doi.org/10.1007/978-94-011-3046-2]
[82]
Abe A, Yamashita S, Noma A. Sensitive, direct colorimetric assay for copper in serum. Clin Chem 1989; 35(4): 552-4.
[http://dx.doi.org/10.1093/clinchem/35.4.552] [PMID: 2702740]
[83]
Squitti R, Lupoi D, Pasqualetti P, et al. Elevation of serum copper levels in Alzheimer’s disease. Neurology 2002; 59(8): 1153-61.
[http://dx.doi.org/10.1212/WNL.59.8.1153] [PMID: 12391342]
[84]
Noubah AM, al-Awqati MA. Ultrafiltrable copper and related analytes in maternal and cord blood. Clin Chem 1990; 36(6): 860-4.
[http://dx.doi.org/10.1093/clinchem/36.6.860] [PMID: 2357822]
[85]
Kupila-Rantala T, Dabek JT, Hyvönen-Dabek M. A high resolution PIXE measurement for blood plasma ultrafiltrate. Application to loosely bound copper. Biol Trace Elem Res 1996; 55(1-2): 173-9.
[http://dx.doi.org/10.1007/BF02784178] [PMID: 8971364]
[86]
Favier A, Ruffieux D. Simple assay of serum copper fractions by ultrafiltration and flameless atomic absorption. Biol Trace Elem Res 1988; 18: 145-60.
[http://dx.doi.org/10.1007/BF02917499] [PMID: 2484560]
[87]
Bohrer D, Do Nascimento PC, Ramirez AG, Mendonça JK, De Carvalho LM, Pomblum SC. Comparison of ultrafiltration and solid phase extraction for the separation of free and protein-bound serum copper for the Wilson’s disease diagnosis. Clin Chim Acta 2004; 345(1-2): 113-21.
[http://dx.doi.org/10.1016/j.cccn.2004.03.001] [PMID: 15193985]
[88]
Inagaki K, Mikuriya N, Morita S, et al. Speciation of protein-binding zinc and copper in human blood serum by chelating resin pre-treatment and inductively coupled plasma mass spectrometry. Analyst (Lond) 2000; 125(1): 197-203.
[http://dx.doi.org/10.1039/a907088e] [PMID: 10885075]
[89]
Venelinov TI, Davies IM, Beattie JH. Dialysis-Chelex method for determination of exchangeable copper in human plasma. Anal Bioanal Chem 2004; 379(5-6): 777-80.
[http://dx.doi.org/10.1007/s00216-004-2529-x] [PMID: 14991216]
[90]
Brewer GJ, Kaur S. Zinc deficiency and zinc therapy efficacy with reduction of serum free copper in Alzheimer’s disease. Int J Alzheimers Dis 2013; 2013: 586365.
[http://dx.doi.org/10.1155/2013/586365] [PMID: 24224111]
[91]
Babiloni C, Squitti R, Del Percio C, et al. Free copper and resting temporal EEG rhythms correlate across healthy, mild cognitive impairment, and Alzheimer’s disease subjects. Clin Neurophysiol 2007; 118(6): 1244-60.
[http://dx.doi.org/10.1016/j.clinph.2007.03.016] [PMID: 17462944]
[92]
Salustri C, Barbati G, Ghidoni R, et al. Is cognitive function linked to serum free copper levels? A cohort study in a normal population. Clin Neurophysiol 2010; 121(4): 502-7.
[http://dx.doi.org/10.1016/j.clinph.2009.11.090] [PMID: 20097602]
[93]
Arnal N, Cristalli DO, de Alaniz MJ, Marra CA. Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives. Brain Res 2010; 1319: 118-30.
[http://dx.doi.org/10.1016/j.brainres.2009.11.085] [PMID: 20026314]
[94]
Rembach A, Doecke JD, Roberts BR, et al. Longitudinal analysis of serum copper and ceruloplasmin in Alzheimer’s disease. J Alzheimers Dis 2013; 34(1): 171-82.
[http://dx.doi.org/10.3233/JAD-121474] [PMID: 23168449]
[95]
Squitti R, Ventriglia M, Barbati G, et al. ‘Free’ copper in serum of Alzheimer’s disease patients correlates with markers of liver function. J Neural Transm (Vienna) 2007; 114(12): 1589-94.
[http://dx.doi.org/10.1007/s00702-007-0777-6] [PMID: 17641816]
[96]
Twomey PJ, Viljoen A, House IM, Reynolds TM, Wierzbicki AS. Relationship between serum copper, ceruloplasmin, and non-ceruloplasmin-bound copper in routine clinical practice. Clin Chem 2005; 51(8): 1558-9.
[http://dx.doi.org/10.1373/clinchem.2005.052688] [PMID: 16040861]
[97]
Twomey PJ, Viljoen A, House IM, Reynolds TM, Wierzbicki AS. Adjusting copper concentrations for caeruloplasmin levels in routine clinical practice. J Clin Pathol 2006; 59(8): 867-9.
[http://dx.doi.org/10.1136/jcp.2005.034876] [PMID: 16644878]
[98]
Twomey PJ, Viljoen A, House IM, Reynolds TM, Wierzbicki AS. Copper:caeruloplasmin ratio. J Clin Pathol 2007; 60(4): 441-2.
[http://dx.doi.org/10.1136/jcp.2006.041756] [PMID: 17405985]
[99]
Twomey PJ, Viljoen A, House IM, Reynolds TM, Wierzbicki AS. Limitations of non-ceruloplasmin-bound copper in routine clinical practice. Gut 2007; 56(1): 154.
[PMID: 17172594]
[100]
Twomey PJ, Wierzbicki AS, House IM, Viljoen A, Reynolds TM. Percentage non-caeruloplasmin bound copper. Clin Biochem 2007; 40(9-10): 749-50.
[http://dx.doi.org/10.1016/j.clinbiochem.2007.04.002] [PMID: 17498678]
[101]
Twomey PJ, Wierzbicki AS, Reynolds TM, Viljoen A. The copper/caeruloplasmin ratio in routine clinical practice in different laboratories. J Clin Pathol 2009; 62(1): 60-3.
[http://dx.doi.org/10.1136/jcp.2007.055111] [PMID: 19103863]
[102]
Buckley WT, Vanderpool RA. Analytical variables affecting exchangeable copper determination in blood plasma. Biometals 2008; 21(6): 601-12.
[http://dx.doi.org/10.1007/s10534-008-9146-7] [PMID: 18546054]
[103]
El Balkhi S, Poupon J, Trocello JM, et al. Determination of ultrafiltrable and exchangeable copper in plasma: stability and reference values in healthy subjects. Anal Bioanal Chem 2009; 394(5): 1477-84.
[http://dx.doi.org/10.1007/s00216-009-2809-6] [PMID: 19421744]
[104]
Squitti R, Siotto M, Ivanova I, Rongioletti M. ATP7B and Alzheimer disease. In: Clinical and translational perspectives on Wilson disease. 2018.
[105]
Squitti R, Siotto M, Arciello M, Rossi L. Non-ceruloplasmin bound copper and ATP7B gene variants in Alzheimer’s disease. Metallomics 2016; 8(9): 863-73.
[http://dx.doi.org/10.1039/C6MT00101G] [PMID: 27499330]
[106]
Rozzini L, Lanfranchi F, Pilotto A, et al. Serum non-ceruloplasmin non-albumin copper elevation in mild cognitive impairment and dementia due to Alzheimer’s disease: A case control study. J Alzheimers Dis 2018; 61(3): 907-12.
[http://dx.doi.org/10.3233/JAD-170552] [PMID: 29332043]
[107]
Catalani S, Paganelli M, Gilberti ME, et al. Free copper in serum: An analytical challenge and its possible applications. J Trace Elem Med Biol 2018; 45: 176-80.
[http://dx.doi.org/10.1016/j.jtemb.2017.11.006] [PMID: 29173476]
[108]
Boll MC, Alcaraz-Zubeldia M, Montes S, Rios C. 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 2008; 33(9): 1717-23.
[http://dx.doi.org/10.1007/s11064-008-9610-3] [PMID: 18307039]
[109]
Guillaud O, Brunet AS, Mallet I, et al. Relative exchangeable copper: A valuable tool for the diagnosis of Wilson disease. Liver Int 2018; 38(2): 350-7.
[http://dx.doi.org/10.1111/liv.13520] [PMID: 28719006]
[110]
Squitti R, Mendez A, Ricordi C, Siotto M, Goldberg R. Copper in glucose intolerance, cognitive decline, and Alzheimer disease. Alzheimer Dis Assoc Disord 2019; 33(1): 77-85.
[http://dx.doi.org/10.1097/WAD.0000000000000280] [PMID: 30640257]
[111]
Ajsuvakova OP, Tinkov AA, Willkommen D, et al. Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson’s disease: A pilot study. J Trace Elem Med Biol 2020; 59: 126423.
[http://dx.doi.org/10.1016/j.jtemb.2019.126423] [PMID: 31733982]
[112]
Solovyev N, Ala A, Schilsky M, Mills C, Willis K, Harrington CF. Biomedical copper speciation in relation to Wilson’s disease using strong anion exchange chromatography coupled to triple quadrupole inductively coupled plasma mass spectrometry. Anal Chim Acta 2020; 1098: 27-36.
[http://dx.doi.org/10.1016/j.aca.2019.11.033] [PMID: 31948584]

Rights & Permissions Print Cite
Article Metrics
29
1
© 2024 Bentham Science Publishers | Privacy Policy