Interactions of metals and apolipoprotein e in Alzheimer's disease

Frontiers in Aging Neuroscience

Volumn 6, Issue JUN, 2014, Pages

  Xu, He ^a   Finkelstein, David I ^a   Adlard, Paul A ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Alzheimer's disease; Apolipoprotein E; Copper; Metals; Zinc

Indexed keywords

ABC TRANSPORTER A1; AMYLOID BETA PROTEIN; APOLIPOPROTEIN A; APOLIPOPROTEIN B; APOLIPOPROTEIN E; APOLIPOPROTEIN E3; APOLIPOPROTEIN E4; COPPER ION; CYCLIN DEPENDENT KINASE 5; METAL ION; TAU PROTEIN; UNCLASSIFIED DRUG; ZINC ION; ZINC TRANSPORTER; ZINC TRANSPORTER 3;

ALZHEIMER DISEASE; BRAIN NERVE CELL; DISEASE ASSOCIATION; DISEASE PREDISPOSITION; ENZYME ACTIVATION; HIPPOCAMPUS; HOMEOSTASIS; HUMAN; LONG TERM POTENTIATION; MEMORY DISORDER; METAL BINDING; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; PROTEIN AGGREGATION; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; REVIEW; SENILE PLAQUE;

EID: 84904582549     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2014.00121     Document Type: Review

References (100)

1. Adlard, P. A., and Bush, A. I. (2006). Metals and Alzheimer's disease. J. Alzheimers Dis. 10, 145-163.
2. Adlard, P. A., Parncutt, J. M., Finkelstein, D. I., and Bush, A. I. (2010). Cognitive loss in zinc transporter-3 knock-out mice: a phenocopy for the synaptic and memory deficits of Alzheimer's disease? J. Neurosci. 30, 1631-1636. doi: 10.1523/jneurosci.5255-09.2010
3. Altamura, S., and Muckenthaler, M. U. (2009). Iron toxicity in diseases of aging: Alzheimer's disease, Parkinson's disease and atherosclerosis. J. Alzheimers Dis. 16, 879-895. doi: 10.3233/JAD-2009-1010
4. Andrews-Zwilling, Y., Bien-Ly, N., Xu, Q., Li, G., Bernardo, A., Yoon, S. Y., et al. (2010). Apolipoprotein E4 causes age- and Tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice. J. Neurosci. 30, 13707-13717. doi: 10.1523/jneurosci.4040-10.2010
5. Ayton, S., Lei, P., and Bush, A. I. (2013). Metallostasis in Alzheimer's disease. Free Radic. Biol. Med. 62, 76-89. doi: 10.1016/j.freeradbiomed.2012.10.558
6. Bertram, L. (2009). Alzheimer's disease genetics current status and future perspectives. Int. Rev. Neurobiol. 84, 167-184. doi: 10.1016/S0074-7742(09)00409-7
7. Brecht, W. J., Harris, F. M., Chang, S., Tesseur, I., Yu, G. Q., Xu, Q., et al. (2004). Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J. Neurosci. 24, 2527-2534. doi: 10.1523/jneurosci.4315-03.2004
8. Brewer, G. J., Dick, R. D., Johnson, V. D., Brunberg, J. A., Kluin, K. J., Fink, J. K., et al. (1998). Treatment of Wilson's disease with zinc: XV long-term follow-up studies. J. Lab. Clin. Med. 132, 264-278. doi: 10.1016/s0022-2143(98)90039-7
9. Bu, G. (2009). Apolipoprotein E and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy. Nat. Rev. Neurosci. 10, 333-344. doi: 10.1038/nrn2620
10. Bush, A. I., and Tanzi, R. E. (2008). Therapeutics for Alzheimer's disease based on the metal hypothesis. Neurotherapeutics 5, 421-432. doi: 10.1016/j.nurt.2008.05.001
11. Caselli, R. J., Reiman, E. M., Locke, D. E., Hutton, M. L., Hentz, J. G., Hoffman-Snyder, C., et al. (2007). Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Arch. Neurol. 64, 1306-1311. doi: 10.1001/archneur.64.9.1306
12. Caselli, R. J., Reiman, E. M., Osborne, D., Hentz, J. G., Baxter, L. C., Hernandez, J. L., et al. (2004). Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele. Neurology 62, 1990-1995. doi: 10.1212/01.wnl.0000129533.26544.bf
13. Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., et al. (2011). Human apoE isoforms differentially regulate brain amyloid-beta peptide clearance. Sci. Transl. Med. 3:89ra57. doi: 10.1126/scitranslmed.3002156
14. Chen, J., Li, Q., and Wang, J. (2011). Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. Proc. Natl. Acad. Sci. U S A 108, 14813-14818. doi: 10.1073/pnas.1106420108
15. Corder, E. H., Saunders, A. M., Risch, N. J., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C. Jr., et al. (1994). Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat. Genet. 7, 180-184. doi: 10.1038/ng0694-180
16. Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., et al. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261, 921-923. doi: 10.1126/science.8346443
17. Cui, L., Schoene, N. W., Zhu, L., Fanzo, J. C., Alshatwi, A., and Lei, K. Y. (2002). Zinc depletion reduced Egr-1 and HNF-3beta expression and apolipoprotein A-I promoter activity in Hep G2 cells. Am. J. Physiol. Cell Physiol. 283, C623-C630. doi: 10.1152/ajpcell.00308.2001
18. Deane, R., and Zlokovic, B. V. (2007). Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease. Curr. Alzheimer Res. 4, 191-197. doi: 10.2174/156720507780362245
19. Duce, J. A., and Bush, A. I. (2010). Biological metals and Alzheimer's disease: implications for therapeutics and diagnostics. Prog. Neurobiol. 92, 1-18. doi: 10.1016/j.pneurobio.2010.04.003
20. Dumanis, S. B., DiBattista, A. M., Miessau, M., Moussa, C. E., and Rebeck, G. W. (2013). APOE genotype affects the pre-synaptic compartment of glutamatergic nerve terminals. J. Neurochem. 124, 4-14. doi: 10.1111/j.1471-4159.2012.07908.x
21. Fagan, A. M., Watson, M., Parsadanian, M., Bales, K. R., Paul, S. M., and Holtzman, D. M. (2002). Human and murine ApoE markedly alters A beta metabolism before and after plaque formation in a mouse model of Alzheimer's disease. Neurobiol. Dis. 9, 305-318. doi: 10.1006/nbdi.2002.0483
22. Fagan, A. M., Younkin, L. H., Morris, J. C., Fryer, J. D., Cole, T. G., Younkin, S. G., et al. (2000). Differences in the Abeta40/Abeta42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype. Ann. Neurol. 48, 201-210. doi: 10.1002/1531-8249(200008)48:2<201::aid-ana10>3.3.co;2-o
23. Frieden, C., and Garai, K. (2012). Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer's disease. Proc. Natl. Acad. Sci. U S A 109, 8913-8918. doi: 10.1073/pnas.1207022109
24. Fryer, J. D., Demattos, R. B., McCormick, L. M., O'Dell, M. A., Spinner, M. L., Bales, K. R., et al. (2005a). The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice. J. Biol. Chem. 280, 25754-25759. doi: 10.1074/jbc.m502143200
25. Fryer, J. D., Simmons, K., Parsadanian, M., Bales, K. R., Paul, S. M., Sullivan, P. M., et al. (2005b). Human apolipoprotein E4 alters the amyloid-beta 40,42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model. J. Neurosci. 25, 2803-2810. doi: 10.1523/jneurosci.5170-04.2005
26. Grasso, G., Giuffrida, M. L., and Rizzarelli, E. (2012). Metallostasis and amyloid beta-degrading enzymes. Metallomics 4, 937-949. doi: 10.1039/c2mt20105d
27. Greenough, M. A., Camakaris, J., and Bush, A. I. (2013). Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Neurochem. Int. 62, 540-555. doi: 10.1016/j.neuint.2012.08.014
28. Guo, C., Wang, P., Zhong, M. L., Wang, T., Huang, X. S., Li, J. Y., et al. (2013). Deferoxamine inhibits iron induced hippocampal tau phosphorylation in the Alzheimer transgenic mouse brain. Neurochem. Int. 62, 165-172. doi: 10.1016/j.neuint.2012.12.005
29. Gupta, V. B., Laws, S. M., Villemagne, V. L., Ames, D., Bush, A. I., Ellis, K. A., et al. (2011). Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging. Neurology 76, 1091-1098. doi: 10.1212/WNL.0b013e318211c352
30. Hara, M., Matsushima, T., Satoh, H., Iso-o, N., Noto, H., Togo, M., et al. (2003). Isoform-dependent cholesterol efflux from macrophages by apolipoprotein E is modulated by cell surface proteoglycans. Arterioscler. Thromb. Vasc. Biol. 23, 269-274. doi: 10.1161/01.atv.0000054199.78458.4b
31. Harris, F. M., Brecht, W. J., Xu, Q., Mahley, R. W., and Huang, Y. (2004). Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase: modulation by zinc. J. Biol. Chem. 279, 44795-44801. doi: 10.1074/jbc.m408127200
32. Harris, F. M., Brecht, W. J., Xu, Q., Tesseur, I., Kekonius, L., Wyss-Coray, T., et al. (2003). Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer's disease-like neurodegeneration and behavioral deficits in transgenic mice. Proc. Natl. Acad. Sci. U S A 100, 10966-10971. doi: 10.1073/pnas.1434398100
33. Hatters, D. M., Zhong, N., Rutenber, E., and Weisgraber, K. H. (2006). Amino-terminal domain stability mediates apolipoprotein E aggregation into neurotoxic fibrils. J. Mol. Biol. 361, 932-944. doi: 10.1016/j.jmb.2006.06.080
34. Hirsch-Reinshagen, V., Zhou, S., Burgess, B. L., Bernier, L., McIsaac, S. A., Chan, J. Y., et al. (2004). Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J. Biol. Chem. 279, 41197-41207. doi: 10.1074/jbc.m407962200
35. Hoke, D. E., Tan, J. L., Ilaya, N. T., Culvenor, J. G., Smith, S. J., White, A. R., et al. (2005). In vitro gamma-secretase cleavage of the Alzheimer's amyloid precursor protein correlates to a subset of presenilin complexes and is inhibited by zinc. FEBS J. 272, 5544-5557. doi: 10.1111/j.1742-4658.2005.04950.x
36. Holtzman, D. M., Herz, J., and Bu, G. (2012). Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. Cold Spring Harb. Perspect. Med. 2:a006312. doi: 10.1101/cshperspect.a006312
37. Hozumi, I., Hasegawa, T., Honda, A., Ozawa, K., Hayashi, Y., Hashimoto, K., et al. (2011). Patterns of levels of biological metals in CSF differ among neurodegenerative diseases. J. Neurol. Sci. 303, 95-99. doi: 10.1016/j.jns.2011.01.003
38. Huang, Y., Liu, X. Q., Wyss-Coray, T., Brecht, W. J., Sanan, D. A., and Mahley, R. W. (2001). Apolipoprotein E fragments present in Alzheimer's disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons. Proc. Natl. Acad. Sci. U S A 98, 8838-8843. doi: 10.1073/pnas.151254698
39. Hung, Y. H., Bush, A. I., and Cherny, R. A. (2010). Copper in the brain and Alzheimer's disease. J. Biol. Inorg. Chem. 15, 61-76. doi: 10.1007/s00775-009-0600-y
40. Hung, Y. H., Bush, A. I., and La Fontaine, S. (2013). Links between copper and cholesterol in Alzheimer's disease. Front. Physiol. 4:111. doi: 10.3389/fphys.2013.00111
41. Iqbal, K., Liu, F., Gong, C. X., and Grundke-Iqbal, I. (2010). Tau in Alzheimer disease and related tauopathies. Curr. Alzheimer Res. 7, 656-664. doi: 10.2174/156720510793611592
42. Jones, N. (2010). Alzheimer disease: plasma clusterin predicts degree of pathogenesis in AD. Nat. Rev. Neurol. 6, 469. doi: 10.1038/nrneurol.2010.122
43. Jones, P. B., Adams, K. W., Rozkalne, A., Spires-Jones, T. L., Hshieh, T. T., Hashimoto, T., et al. (2011). Apolipoprotein E: isoform specific differences in tertiary structure and interaction with amyloid-beta in human Alzheimer brain. PLoS One 6:e14586. doi: 10.1371/journal.pone.0014586
44. Karlin, S., and Zhu, Z. Y. (1997). Classification of mononuclear zinc metal sites in protein structures. Proc. Natl. Acad. Sci. U S A 94, 14231-14236. doi: 10.1073/pnas.94.26.14231
45. Kim, J., Basak, J. M., and Holtzman, D. M. (2009). The role of apolipoprotein E in Alzheimer's disease. Neuron 63, 287-303. doi: 10.1016/j.neuron.2009.06.026
46. Kitazawa, M., Cheng, D., and Laferla, F. M. (2009). Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. J. Neurochem. 108, 1550-1560. doi: 10.1111/j.1471-4159.2009.05901.x
47. Kok, E., Haikonen, S., Luoto, T., Huhtala, H., Goebeler, S., Haapasalo, H., et al. (2009). Apolipoprotein E-dependent accumulation of Alzheimer disease-related lesions begins in middle age. Ann. Neurol. 65, 650-657. doi: 10.1002/ana.21696
48. Lammich, S., Kojro, E., Postina, R., Gilbert, S., Pfeiffer, R., Jasionowski, M., et al. (1999). Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease. Proc. Natl. Acad. Sci. U S A 96, 3922-3927. doi: 10.1073/pnas.96.7.3922
49. Lee, J. Y., Cho, E., Kim, T. Y., Kim, D. K., Palmiter, R. D., Volitakis, I., et al. (2010). Apolipoprotein E ablation decreases synaptic vesicular zinc in the brain. Biometals 23, 1085-1095. doi: 10.1007/s10534-010-9354-9
50. Lei, P., Ayton, S., Bush, A. I., and Adlard, P. A. (2011). GSK-3 in neurodegenerative diseases. Int. J. Alzheimers Dis. 2011:189246. doi: 10.4061/2011/189246
51. Linkous, D. H., Flinn, J. M., Koh, J. Y., Lanzirotti, A., Bertsch, P. M., Jones, B. F., et al. (2008). Evidence that the ZNT3 protein controls the total amount of elemental zinc in synaptic vesicles. J. Histochem. Cytochem. 56, 3-6. doi: 10.1369/jhc.6a7035.2007
52. Liu, Q., Trotter, J., Zhang, J., Peters, M. M., Cheng, H., Bao, J., et al. (2010). Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J. Neurosci. 30, 17068-17078. doi: 10.1523/JNEUROSCI.4067-10.2010
53. Liu, Q., Zerbinatti, C. V., Zhang, J., Hoe, H. S., Wang, B., Cole, S. L., et al. (2007). Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron 56, 66-78. doi: 10.1016/j.neuron.2007.08.008
54. Lovell, M. A., Robertson, J. D., Teesdale, W. J., Campbell, J. L., and Markesbery, W. R. (1998). Copper, iron and zinc in Alzheimer's disease senile plaques. J. Neurol. Sci. 158, 47-52. doi: 10.1016/s0022-510x(98)00092-6
55. Mahley, R. W., and Huang, Y. (2006). Apolipoprotein (apo) E4 and Alzheimer's disease: unique conformational and biophysical properties of apoE4 can modulate neuropathology. Acta Neurol. Scand. Suppl. 185, 8-14. doi: 10.1111/j.1600-0404.2006.00679.x
56. Mahley, R. W., Rall, S. C.Jr (2000). Apolipoprotein E: far more than a lipid transport protein. Annu. Rev. Genomics Hum. Genet. 1, 507-537. doi: 10.1146/annurev.genom.1.1.507
57. Martic, S., Rains, M. K., and Kraatz, H. B. (2013). Probing copper/tau protein interactions electrochemically. Anal. Biochem. 442, 130-137. doi: 10.1016/j.ab.2013.07.015
58. Mauch, D. H., Nagler, K., Schumacher, S., Goritz, C., Muller, E. C., Otto, A., et al. (2001). CNS synaptogenesis promoted by glia-derived cholesterol. Science 294, 1354-1357. doi: 10.1126/science.294.5545.1354
59. Michikawa, M., Fan, Q. W., Isobe, I., and Yanagisawa, K. (2000). Apolipoprotein E exhibits isoform-specific promotion of lipid efflux from astrocytes and neurons in culture. J. Neurochem. 74, 1008-1016. doi: 10.1046/j.1471-4159.2000.0741008.x
60. Miyata, M., and Smith, J. D. (1996). Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nat. Genet. 14, 55-61. doi: 10.1038/ng0996-55
61. Moir, R. D., Atwood, C. S., Romano, D. M., Laurans, M. H., Huang, X., Bush, A. I., et al. (1999). Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta using physiological concentrations. Biochemistry 38, 4595-4603. doi: 10.1021/bi982437d
62. Morante, S. (2008). The role of metals in beta-amyloid peptide aggregation: X-Ray spectroscopy and numerical simulations. Curr. Alzheimer Res. 5, 508-524. doi: 10.2174/156720508786898505
63. Morris, M., Maeda, S., Vossel, K., and Mucke, L. (2011). The many faces of tau. Neuron 70, 410-426. doi: 10.1016/j.neuron.2011.04.009
64. Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., et al. (2010). APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging. Ann. Neurol. 67, 122-131. doi: 10.1002/ana.21843
65. Morrow, J. A., Hatters, D. M., Lu, B., Hochtl, P., Oberg, K. A., Rupp, B., et al. (2002). Apolipoprotein E4 forms a molten globule. A potential basis for its association with disease. J. Biol. Chem. 277, 50380-50385. doi: 10.1074/jbc.m204898200
66. Mulder, M., Jansen, P. J., Janssen, B. J., van de Berg, W. D., van der Boom, H., Havekes, L. M., et al. (2004). Low-density lipoprotein receptor-knockout mice display impaired spatial memory associated with a decreased synaptic density in the hippocampus. Neurobiol. Dis. 16, 212-219. doi: 10.1016/j.nbd.2004.01.015
67. Namba, Y., Tomonaga, M., Kawasaki, H., Otomo, E., and Ikeda, K. (1991). Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease. Brain Res. 541, 163-166. doi: 10.1016/0006-8993(91)91092-f
68. Narayanaswami, V., Maiorano, J. N., Dhanasekaran, P., Ryan, R. O., Phillips, M. C., Lund-Katz, S., et al. (2004). Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles. J. Biol. Chem. 279, 14273-14279. doi: 10.1074/jbc.m313318200
69. Noda, Y., Asada, M., Kubota, M., Maesako, M., Watanabe, K., Uemura, M., et al. (2013). Copper enhances APP dimerization and promotes Abeta production. Neurosci. Lett. 547, 10-15. doi: 10.1016/j.neulet.2013.04.057
70. Pa, J., Boxer, A., Chao, L. L., Gazzaley, A., Freeman, K., Kramer, J., et al. (2009). Clinical-neuroimaging characteristics of dysexecutive mild cognitive impairment. Ann. Neurol. 65, 414-423. doi: 10.1002/ana.21591
71. Pan, E., Zhang, X. A., Huang, Z., Krezel, A., Zhao, M., Tinberg, C. E., et al. (2011). Vesicular zinc promotes presynaptic and inhibits postsynaptic long-term potentiation of mossy fiber-CA3 synapse. Neuron 71, 1116-1126. doi: 10.1016/j.neuron.2011.07.019
72. Paoletti, P., Vergnano, A. M., Barbour, B., and Casado, M. (2009). Zinc at glutamatergic synapses. Neuroscience 158, 126-136. doi: 10.1016/j.neuroscience.2008.01.061
73. Pfrieger, F. W. (2003). Cholesterol homeostasis and function in neurons of the central nervous system. Cell. Mol. Life Sci. 60, 1158-1171.
74. Reaves, S. K., Wu, J. Y., Wu, Y., Fanzo, J. C., Wang, Y. R., Lei, P. P., et al. (2000). Regulation of intestinal apolipoprotein B mRNA editing levels by a zinc-deficient diet and cDNA cloning of editing protein in hamsters. J. Nutr. 130, 2166-2173.
75. Rebeck, G. W., Reiter, J. S., Strickland, D. K., and Hyman, B. T. (1993). Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron 11, 575-580. doi: 10.1016/0896-6273(93)90070-8
76. Riddell, D. R., Zhou, H., Atchison, K., Warwick, H. K., Atkinson, P. J., Jefferson, J., et al. (2008). Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels. J. Neurosci. 28, 11445-11453. doi: 10.1523/JNEUROSCI.1972-08.2008
77. Rosenblum, W. I. (2014). Why Alzheimer trials fail: removing soluble oligomeric beta amyloid is essential, inconsistent and difficult. Neurobiol. Aging 35, 969-974. doi: 10.1016/j.neurobiolaging.2013.10.085
78. Sayre, L. M., Perry, G., Harris, P. L., Liu, Y., Schubert, K. A., and Smith, M. A. (2000). In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals. J. Neurochem. 74, 270-279. doi: 10.1046/j.1471-4159.2000.0740270.x
79. Smith, G. E., Bohac, D. L., Waring, S. C., Kokmen, E., Tangalos, E. G., Ivnik, R. J., et al. (1998). Apolipoprotein E genotype influences cognitive 'phenotype' in patients with Alzheimer's disease but not in healthy control subjects. Neurology 50, 355-362. doi: 10.1212/wnl.50.2.355
80. Spoerri, L., Vella, L. J., Pham, C. L., Barnham, K. J., and Cappai, R. (2012). The amyloid precursor protein copper binding domain histidine residues 149 and 151 mediate APP stability and metabolism. J. Biol. Chem. 287, 26840-26853. doi: 10.1074/jbc.m112.355743
81. Squitti, R., Barbati, G., Rossi, L., Ventriglia, M., Dal Forno, G., Cesaretti, S., et al. (2006). Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF [beta]-amyloid and h-tau. Neurology 67, 76-82. doi: 10.1212/01.wnl.0000223343.82809.cf
82. Squitti, R., Bressi, F., Pasqualetti, P., Bonomini, C., Ghidoni, R., Binetti, G., et al. (2009). Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology 72, 50-55. doi: 10.1212/01.wnl.0000338568.28960.3f
83. Squitti, R., Simonelli, I., Ventriglia, M., Siotto, M., Pasqualetti, P., Rembach, A., et al. (2014). Meta-analysis of serum non-ceruloplasmin copper in Alzheimer's disease. J. Alzheimers Dis. 38, 809-822. doi: 10.3233/JAD-131247
84. Strittmatter, W. J., Weisgraber, K. H., Goedert, M., Saunders, A. M., Huang, D., Corder, E. H., et al. (1994). Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Exp. Neurol. 125, 163-171; discussion 172-164. doi: 10.1006/exnr.1994.1019
85. Tokuda, T., Calero, M., Matsubara, E., Vidal, R., Kumar, A., Permanne, B., et al. (2000). Lipidation of apolipoprotein E influences its isoform-specific interaction with Alzheimer's amyloid beta peptides. Biochem. J. 348(Pt. 2), 359-365. doi: 10.1042/0264-6021:3480359
86. Tõugu, V., Karafin, A., Zovo, K., Chung, R. S., Howells, C., West, A. K., et al. (2009). Zn(II)- and Cu(II)-induced non-fibrillar aggregates of amyloid-beta (1-42) peptide are transformed to amyloid fibrils, both spontaneously and under the influence of metal chelators. J. Neurochem. 110, 1784-1795. doi: 10.1111/j.1471-4159.2009.06269.x
87. Trougakos, I. P., Pawelec, G., Tzavelas, C., Ntouroupi, T., and Gonos, E. S. (2006). Clusterin/Apolipoprotein J up-regulation after zinc exposure, replicative senescence or differentiation of human haematopoietic cells. Biogerontology 7, 375-382. doi: 10.1007/s10522-006-9052-8
88. Verghese, P. B., Castellano, J. M., and Holtzman, D. M. (2011). Apolipoprotein E in Alzheimer's disease and other neurological disorders. Lancet Neurol. 10, 241-252. doi: 10.1016/s1474-4422(10)70325-2
89. Vural, H., Demirin, H., Kara, Y., Eren, I., and Delibas, N. (2010). Alterations of plasma magnesium, copper, zinc, iron and selenium concentrations and some related erythrocyte antioxidant enzyme activities in patients with Alzheimer's disease. J. Trace Elem. Med. Biol. 24, 169-173. doi: 10.1016/j.jtemb.2010.02.002
90. Wahrle, S. E., Jiang, H., Parsadanian, M., Kim, J., Li, A., Knoten, A., et al. (2008). Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J. Clin. Invest. 118, 671-682. doi: 10.1172/jci33622
91. Wahrle, S. E., Jiang, H., Parsadanian, M., Legleiter, J., Han, X., Fryer, J. D., et al. (2004). ABCA1 is required for normal central nervous system ApoE levels and for lipidation of astrocyte-secreted apoE. J. Biol. Chem. 279, 40987-40993. doi: 10.1074/jbc.m407963200
92. Wang, C., Vernon, R., Lange, O., Tyka, M., and Baker, D. (2010). Prediction of structures of zinc-binding proteins through explicit modeling of metal coordination geometry. Protein Sci. 19, 494-506. doi: 10.1002/pro.327
93. Wärmländer, S., Tiiman, A., Abelein, A., Luo, J., Jarvet, J., Söderberg, K. L., et al. (2013). Biophysical studies of the amyloid beta-peptide: interactions with metal ions and small molecules. Chembiochem 14, 1692-1704. doi: 10.1002/cbic.201300262
94. Weisgraber, K. H., Roses, A. D., and Strittmatter, W. J. (1994). The role of apolipoprotein E in the nervous system. Curr. Opin. Lipidol. 5, 110-116. doi: 10.1097/00041433-199404000-00007
95. White, A. R., Reyes, R., Mercer, J. F., Camakaris, J., Zheng, H., Bush, A. I., et al. (1999). Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res. 842, 439-444. doi: 10.1016/s0006-8993(99)01861-2
96. Wildsmith, K. R., Holley, M., Savage, J. C., Skerrett, R., and Landreth, G. E. (2013). Evidence for impaired amyloid beta clearance in Alzheimer's disease. Alzheimers Res. Ther. 5, 33. doi: 10.1186/alzrt187
97. Xiong, Y., Jing, X. P., Zhou, X. W., Wang, X. L., Yang, Y., Sun, X. Y., et al. (2013). Zinc induces protein phosphatase 2A inactivation and tau hyperphosphorylation through Src dependent PP2A (tyrosine 307) phosphorylation. Neurobiol. Aging 34, 745-756. doi: 10.1016/j.neurobiolaging.2012.07.003
98. Zhang, J. J., Wang, Y., and Lei, K. Y. (1995). Apolipoprotein A-I synthesis and secretion are increased in Hep G2 cells depleted of copper by cupruretic tetramine. J. Nutr. 125, 172-182.
99. Zhong, N., and Weisgraber, K. H. (2009). Understanding the association of apolipoprotein E4 with Alzheimer disease: clues from its structure. J. Biol. Chem. 284, 6027-6031. doi: 10.1074/jbc.r800009200
100. Zhou, L. X., Du, J. T., Zeng, Z. Y., Wu, W. H., Zhao, Y. F., Kanazawa, K., et al. (2007). Copper (II) modulates in vitro aggregation of a tau peptide. Peptides 28, 2229-2234. doi: 10.1016/j.peptides.2007.08.022