The role of metal ions in the evolution and progression of Alzheimer’s disease (AD) is becoming increasingly apparent. Indeed, the interactions of age-associated increases in metals with the amyloid precursor protein (APP) and its proteolytic enzymes and subsequent proteolytic fragments (such as -amyloid (A )) are well characterized. Likewise, the metal associated and age-related formation of free radicals, the subsequent generation of oxidative stress and its interactions on process whose dysfunction may contribute to the development of AD have also been highly characterized. Metal dyshomeostasis may thus initiate, and propogate, the development of AD. As science continues to gain greater resolution into the molecular underpinnings of AD, the potential for the use of metal-modulation in the treatment of this disorder is gaining greater acceptance.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
12. References
Abramov, A.Y., Canevari, L. and Duchen, M.R., 2003, Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J. Neurosci. 23: 5088.
Adlard, P.A. and Cummings, B.J., 2004, Alzheimer’s disease - a sum greater than its parts? Neurobiol. Aging 25: 725.
Adlard, P.A., West, A.K. and Vickers, J.C., 1998, Increased density of metallothionein I/II-immunopositive cortical glial cells in the early stages of Alzheimer’s disease. Neurobiol. Dis. 5: 349.
Ahluwalia, N., Gordon, A., Handte, G., Mahlon, M., Li, N.Q., Beard, J.L., Weinstock, D. and Ross, A.C., 2000, Iron status and stores decline with age in Lewis rats. J. Nutr. 130: 2378.
An, W.L., Bjorkdahl, C., Liu, R., Cowburn, R.F., Winblad, B. and Pei, J.J., 2005, Mechanism of zinc-induced phosphorylation of p70 S6 kinase and glycogen synthase kinase 3beta in SH-SY5Y neuroblastoma cells. J. Neurochem. 92: 1104.
Angeletti, B., Waldron, K.J., Freeman, K.B., Bawagan, H., Hussain, I., Miller, C.C., Lau, K.F., Tennant, M.E., Dennison, C., Robinson, N.J. and Dingwall, C., 2005, BACE1 cytoplasmic domain interacts with the copper chaperone for superoxide dismutase-1 and binds copper. J. Biol. Chem. 280: 17930.
Arlt, S., Beisiegel, U. and Kontush, A., 2002, Lipid peroxidation in neurodegeneration: new insights into Alzheimer’s disease. Curr. Opin. Lipidol. 13: 289.
Armendariz, A.D., Gonzalez, M., Loguinov, A.V. and Vulpe, C.D., 2004, Gene expression profiling in chronic copper overload reveals upregulation of Prnp and App. Physiol. Genomics. 20: 45.
Atwood, C.S., Moir, R.D., Huang, X., Scarpa, R.C., Bacarra, N.M., Romano, D.M., Hartshorn, M.A., Tanzi, R.E. and Bush, A.I., 1998, Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions represent-ting physiological acidosis. J. Biol. Chem. 273: 12817.
Atwood, C.S., Huang, X., Khatri, A., Scarpa, R.C., Kim, Y.S., Moir, R.D., Tanzi, R.E., Roher, A.E. and Bush, A.I., 2000a, Copper catalyzed oxidation of Alzheimer Abeta. Cell Mol. Biol. (Noisy-le-grand) 46: 777.
Atwood, C.S., Scarpa, R.C., Huang, X., Moir, R.D., Jones, W.D., Fairlie, D.P., Tanzi, R.E. and Bush, A.I., 2000b, Characterization of copper interactions with alzheimer amyloid beta peptides: identification of an attomolar-affinity copper binding site on amyloid beta1-42. J. Neurochem. 75: 1219.
Atwood, C.S., Perry, G., Zeng, H., Kato, Y., Jones, W.D., Ling, K.Q., Huang, X., Moir, R.D., Wang, D., Sayre, L.M., Smith, M.A., Chen, S.G. and Bush, A.I., 2004, Copper mediates dityrosine cross-linking of Alzheimer’s amyloid-beta. Biochemistry 43: 560.
Augustinack, J.C., Schneider, A., Mandelkow, E.M. and Hyman, B.T., 2002, Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer’s disease. Acta Neuropathol. (Berl). 103: 26.
Barnham, K.J., McKinstry, W.J., Multhaup, G., Galatis, D., Morton, C.J., Curtain, C.C., Williamson, N.A., White, A.R., Hinds, M.G., Norton, R.S., Beyreuther, K., Masters, C.L., Parker, M.W. and Cappai, R., 2003a, Structure of the Alzheimer’s disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis. J. Biol. Chem. 278: 17401.
Barnham, K.J., Ciccotosto, G.D., Tickler, A.K., Ali, F.E., Smith, D.G., Williamson, N.A., Lam, Y.H., Carrington, D., Tew, D., Kocak, G., Volitakis, I., Separovic, F., Barrow, C.J., Wade, J.D., Masters, C.L., Cherny, R.A., Curtain, C.C., Bush, A.I. and Cappai, R., 2003b, Neurotoxic, redox-competent Alzheimer’s beta-amyloid is released from lipid membrane by methionine oxidation. J. Biol. Chem. 278: 42959.
Barnham, K.J., Haeffner, F., Ciccotosto, G.D., Curtain, C.C., Tew, D., Mavros, C., Beyreuther, K., Carrington, D., Masters, C.L., Cherny, R.A., Cappai, R. and Bush, A.I., 2004, Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer’s disease beta-amyloid. FASEB J. 18: 1427.
Basha, M.R., Wei, W., Bakheet, S.A., Benitez, N., Siddiqi, H.K., Ge, Y.W., Lahiri, D.K. and Zawia, N.H., 2005a, The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain. J. Neurosci. 25: 823.
Basha, M.R., Murali, M., Siddiqi, H.K., Ghosal, K., Siddiqi, O.K., Lashuel, H.A., Ge, Y.W., Lahiri, D.K. and Zawia, N.H., 2005b, Lead (Pb) exposure and its effect on APP proteolysis and Abeta aggregation. FASEB J. 19: 2083.
Basun, H.L., Forssell, G., Wetterberg, L. and Winblad, B., 1991, Metals and trace elements in plasma and cerebrospinal fluid in normal aging and Alzheimer’s disease. J. Neural Transm. Park. Dis. Dement. Sect. 3: 231.
Bayer, T.A., Schafer, S., Simons, A., Kemmling, A., Kamer, T., Tepest, R., Eckert, A., Schussel, K., Eikenberg, O., Sturchler-Pierrat, C., Abramowski, D., Staufenbiel, M. and Multhaup, G., 2003, Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice. Proc. Natl. Acad. Sci. USA 100: 14187.
Behl, C., Davis, J.B., Lesley, R. and Schubert, D., 1994, Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77: 817.
Bellingham, S.A., Lahiri, D.K., Maloney, B., La Fontaine, S., Multhaup, G. and Camakaris, J., 2004a, Copper depletion down-regulates expression of the Alzheimer’s disease amyloid-beta precursor protein gene. J. Biol. Chem. 279: 20378.
Bellingham, S.A., Ciccotosto, G.D., Needham, B.E., Fodero, L.R., White, A.R., Masters, C.L., Cappai, R. and Camakaris, J., 2004b, Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons and embryonic fibroblasts. J. Neurochem. 91: 423.
Bishop, G.M., Robinson, S.R., Liu, Q., Perry, G., Atwood, C.S. and Smith, M.A., 2002, Iron: a pathological mediator of Alzheimer disease? Dev. Neurosci. 24: 184.
Bjorkdahl, C., Sjogren, M.J., Winblad, B. and Pei, J.J., 2005, Zinc induces neurofilament phosphorylation independent of p70 S6 kinase in N2a cells. Neuroreport 16: 591.
Blasko, I., Stampfer-Kountchev, M., Robatscher, P., Veerhuis, R., Eikelenboom, P. and Grubeck-Loebenstein, B., 2004, How chronic inflammation can affect the brain and support the development of Alzheimer’s disease in old age: the role of microglia and astrocytes. Aging Cell 3: 169.
Bleecker, M.L., Ford, D.P., Lindgren, K.N., Hoese, V.M., Walsh, K.S. and Vaughan, C.G., 2005, Differential effects of lead exposure on components of verbal memory. Occup. Environ. Med. 62: 181.
Borchardt, T., Camakaris, J., Cappai, R.C., Masters, L., Beyreuther, K. and Multhaup, G., 1999, Copper inhibits beta-amyloid production and stimulates the nonamyloidogenic pathway of amyloid-precursor-protein secretion. Biochem. J. 344: 461.
Bouras, C., Giannakopoulos, P., Good, P.F., Hsu, A., Hof, P.R. and Perl, D.P., 1997, A laser microprobe mass analysis of brain aluminum and iron in dementia pugilistica: comparison with Alzheimer’s disease. Eur. Neurol. 38: 53.
Braak, H., Braak, E., Bohl, J. and Bratzke, H., 1998, Evolution of Alzheimer’s disease related cortical lesions. J. Neural Transm. Suppl. 54: 106.
Brookmeyer, R., Gray, S. and Kawas, C., 1998, Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am. J. Public Health 88: 1337.
Brown, A.M., Tummolo, D.M., Rhodes, K.J., Hofmann, J.R., Jacobsen, J.S. and Sonnenberg-Reines, J., 1997, Selective aggregation of endogenous beta-amyloid peptide and soluble amyloid precursor protein in cerebrospinal fluid by zinc. J. Neurochem. 69: 1204.
Buckley, C.A., Rouhani, F.N., Kaler, M., Adamik, B., Hawari, F.I. and Levine, S.J., 2005, Amino-terminal TACE prodomain attenuates TNFR2 cleavage independently of the cysteine switch. Am. J. Physiol. Lung Cell Mol. Physiol. 288: L1132.
Bunker, V.W., Hinks, L.J., Stansfield, M.F., Lawson, M.S. and Clayton, B.E., 1987, Metabolic balance studies for zinc and copper in housebound elderly people and the relationship between zinc balance and leukocyte zinc concentrations. Am. J. Clin. Nutr. 46: 353.
Bush, A.I., Multhaup, G., Moir, R.D., Williamson, T.G., Small, D.H., Rumble, B., Pollwein, P., Beyreuther, K. and Masters, C.L., 1993, A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer’s disease. J. Biol. Chem. 268: 16109.
Bush, A.I., Pettingell, W.H., Jr., de Paradis, M., Tanzi, R.E. and Wasco, W., 1994a, The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily. J. Biol. Chem. 269: 26618.
Bush, A.I., Pettingell, W.H., Multhaup, G., Paradis, M., Vonsattel, J.P., Gusella, J.F., Beyreuther, K., Masters, C.L. and Tanzi, R.E., 1994b, Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265: 1464.
Bush, A.I., Pettingell, W.H., Jr., Paradis, M.D. and Tanzi, R.E., 1994c, Modulation of A beta adhesiveness and secretase site cleavage by zinc. J. Biol. Chem. 269: 12152.
Butterfield, D.A., Castegna, A., Lauderback, C.M. and Drake, J., 2002, Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Neurobiol. Aging 23: 655.
Buxbaum, J.D., Liu, K.N., Luo, Y., Slack, J.L., Stocking, K.L., Peschon, J.J., Johnson, R.S., Castner, B.J., Cerretti, D.P. and Black, R.A., 1998, Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J. Biol. Chem. 273: 27765.
Caccamo, A., Oddo, S., Sugarman, M.C., Akbari, Y. and LaFerla, F.M., 2005, Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiol. Aging 26: 645.
Cai, H., Wang, Y., McCarthy, D., Wen, H., Borchelt, D.R., Price, D.L. and Wong, P.C., 2001, BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat. Neurosci. 4: 233.
Campbell, A.M., Smith, A., Sayre, L.M., Bondy, S.C. and Perry, G., 2001, Mechanisms by which metals promote events connected to neurodegenerative diseases. Brain Res. Bull. 55: 125.
Cardoso, S.M., Proenca, M.T., Santos, S., Santana, I. and Oliveira, C.R., 2004, Cytochrome c oxidase is decreased in Alzheimer’s disease platelets. Neurobiol. Aging 25: 105.
Carson, J.A. and Turner, A.J., 2002, Beta-amyloid catabolism: roles for neprilysin(NEP) and other metallopeptidases? J. Neurochem. 81: 1.
Cerpa, W., Varela-Nallar, L., Reyes, A.E., Minniti, A.N. and Inestrosa, N.C., 2005, Is there a role for copper in neurodegenerative diseases? Mol. Aspects Med. 26: 405.
Cherny, R.A., Legg, J.T., McLean, C.A., Fairlie, D.P., Huang, X., Atwood, C.S., Beyreuther, K., Tanzi, R.E., Masters, C.L. and Bush, A.I., 1999, Aqueous dissolution of Alzheimer’s disease Abeta amyloid deposits by biometal depletion. J. Biol. Chem. 274: 23223.
Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A., Barnham, K.J., Volitakis, I., Fraser, F.W., Kim, Y., Huang, X., Goldstein, L.E., Moir, R.D., Lim, J., Beyreuther, T.K., Zheng, H., Tanzi, R.E., Masters, C.L. and Bush, A.I., 2001, Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 30: 665.
Chong, M.S. and Sahadevan, S., 2005, Preclinical Alzheimer’s disease: diagnosis and prediction of progression. Lancet Neurol. 4: 576.
Chung, R.S., Adlard, P.A., Dittmann, J., Vickers, J.C., Chuah, M. and West, A., 2004, Neuron-glia communication: metallothionein expression is specifically upregulated by astrocytes in response to neuronal injury. J. Neurochem. 88: 454.
Ciccotosto, G.D., Tew, D., Curtain, C.C., Smith, D., Carrington, D., Masters, C.L., Bush, A.I., Cherny, R.A., Cappai, R. and Barnham, K.J., 2004, Enhanced toxicity and cellular binding of a modified amyloid beta peptide with a methionine to valine substitution. J. Biol. Chem. 279: 42528.
Citron, M., 2004, Strategies for disease modification in Alzheimer’s disease. Nat. Rev. Neurosci. 5: 677.
Ciuculescu, E.D., Mekmouche, Y. and Faller, P., 2005, Metal-binding properties of the peptide APP(170-188): a model of the Zn(II)-binding site of amyloid precursor protein (APP). Chemistry 11: 903.
Coleman, P., Federoff, H. and Kurlan, R., 2004, A focus on the synapse for neuroprotection in Alzheimer’s disease and other dementias. Neurology 63: 1155.
Connor, J.R., Tucker, P., Johnson, M. and Snyder, B., 1993, Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer’s disease. Neurosci. Lett. 159: 88.
Cottrell, D.A., Blakely, E.L., Johnson, M.A., Ince, P.G. and Turnbull, D.M., 2001, Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology 57: 260.
Cross, J.B., Duca, J.S., Kaminski, J.J. and Madison, V.S., 2002, The active site of a zinc-dependent metalloproteinase influences the computed pK(a) of ligands coordinated to the catalytic zinc ion. J. Am. Chem. Soc. 124: 11004.
Cuajungco, M.P., Goldstein, L.E., Nunomura, A., Smith, M.A., Lim, J.T., Atwood, C.S., Huang, X., Farrag, Y.W., Perry, G. and Bush, A.I., 2000, Evidence that the beta-amyloid plaques of Alzheimer’s disease represent the redox-silencing and entombment of abeta by zinc. J. Biol. Chem. 275: 19439.
Curtain, C.C., Ali, F., Volitakis, I., Cherny, R.A., Norton, R.S., Beyreuther, K., Barrow, C.J., Masters, C.L., Bush, A.I. and Barnham, K.J., 2001, Alzheimer’s disease amyloid-beta binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits. J. Biol. Chem. 276: 20466.
Curtain, C.C., Ali, F.E., Smith, D.G., Bush, A.I., Masters, C.L. and Barnham, K.J., 2003, Metal ions, pH, and cholesterol regulate the interactions of Alzheimer’s disease amyloid-beta peptide with membrane lipid. J. Biol. Chem. 278: 2977.
Dahlgren, K.N., Manelli, A.M., Stine, W.B., Jr., Baker, L.K., Krafft, G.A. and LaDu, M.J., 2002, Oligomeric and fibrillar species of amyloid-beta peptides differentially affect neuronal viability. J. Biol. Chem. 277: 32046.
Danscher, G., Jensen, K.B., Frederickson, C.J., Kemp, K., Andreasen, A., Juhl, S., Stoltenberg, M. and Ravid, R., 1997, Increased amount of zinc in the hippocampus and amygdala of Alzheimer’s diseased brains: a proton-induced X-ray emission spectroscopic analysis of cryostat sections from autopsy material. J. Neurosci. Methods 76: 53.
Davis, C.D., Milne, D.B. and Nielsen, F.H., 2000, Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins. Am. J. Clin. Nutr. 71: 781.
De Deyn, P.P., Hiramatsu, M., Borggreve, F., Goeman, J., D’Hooge, R., Saerens, J. and Mori, A., 1998, Superoxide dismutase activity in cerebrospinal fluid of patients with dementia and some other neurological disorders. Alzheimer Dis. Assoc. Disord. 12: 26.
de Silva, R., Lashley, T., Gibb, G., Hanger, D., Hope, A., Reid, A., Bandopadhyay, R., Utton, M., Strand, C., Jowett, T., Khan, N., Anderton, B., Wood, N., Holton, J., Revesz, T. and Lees, A., 2003, Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies. Neuropathol. Appl. Neurobiol. 29: 288.
De Strooper, B., 2003, Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 38: 9.
Deibel, M.A., Ehmann, W.D. and Markesbery, W.R., 1996, Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress. J. Neurol. Sci. 143: 137.
Dermaut, B., Kumar-Singh, S., Engelborghs, S., Theuns, J., Rademakers, R., Saerens, J., Pickut, B.A., Peeters, K., van den Broeck, M., Vennekens, K., Claes, S., Cruts, M., Cras, P., Martin, J.J., Van Broeckhoven, C. and De Deyn, P.P., 2004, A novel presenilin 1 mutation associated with Pick’s disease but not beta-amyloid plaques. Ann. Neurol. 55: 617.
Desai, A.K. and Grossberg, G.T., 2005, Diagnosis and treatment of Alzheimer’s disease. Neurology 64: S34.
Dickson, T.C. and Vickers, J.C., 2001, The morphological phenotype of beta-amyloid plaques and associated neuritic changes in Alzheimer’s disease. Neuroscience 105: 99.
Dong, J., Atwood, C.S., Anderson, V.E., Siedlak, S.L., Smith, M.A., Perry, G. and Carey, P.R., 2003, Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry 42: 2768.
Eagle, G.R., Zombola, R.R. and Himes, R.H., 1983, Tubulin-zinc interactions: binding and polymerization studies. Biochemistry 22: 221.
Egana, J.T., Zambrano, C., Nunez, M.T., Gonzalez-Billault, C. and Maccioni, R.B., 2003, Iron-induced oxidative stress modify tau phosphorylation patterns in hippocampal cell cultures. Biometals 16: 215.
Ekmekcioglu, C., 2001, The role of trace elements for the health of elderly individuals. Nahrung 45: 309.
Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E.A., Frosch, M.P., Eckman, C.B., Tanzi, R.E., Selkoe, D.J. and Guenette, S., 2003, Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. USA 100: 4162.
Ferretti, G., Bacchetti, T., Moroni, C., Vignini, A. and Curatola, G., 2003, Copper-induced oxidative damage on astrocytes: protective effect exerted by human high density lipoproteins. Biochim. Biophys. Acta 1635: 48.
Forbes, W.F. and Hill, G.B., 1998, Is exposure to aluminum a risk factor for the development of Alzheimer’s disease? - Yes. Arch. Neurol. 55: 740.
Frausto da Silva, J.J.R. and Williams, R.J.P., 2001, The Biological Chemistry of the Elements, Oxford University Press, Oxford.
Friedhoff, P., von Bergen, M., Mandelkow, E.M., Davies, P. and Mandelkow, E., 1998, A nucleated assembly mechanism of Alzheimer paired helical filaments. Proc. Natl. Acad. Sci. USA 95: 15712.
Friedhoff, P., von Bergen, M., Mandelkow, E.M. and Mandelkow, E., 2000, Structure of tau protein and assembly into paired helical filaments. Biochim. Biophys. Acta 1502: 122.
Friedlich, A.L., Lee, J.Y., van Groen, T., Cherny, R.A., Volitakis, I., Cole, T.B., Palmiter, R.D., Koh, J.Y. and Bush, A.I., 2004, Neuronal zinc exchange with the blood vessel wall promotes cerebral amyloid angiopathy in an animal model of Alzheimer’s disease. J. Neurosci. 24: 3453.
Frisoni, G.B., Padovani, A. and Wahlund, L.O., 2004, The predementia diagnosis of Alzheimer’s disease. Alzheimer Dis. Assoc. Disord. 18: 51.
Gabbita, S.P., Lovell, M.A. and Markesbery, W.R., 1998, Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J. Neurochem. 71: 2034.
Gandy, S., 2005, The role of cerebral amyloid beta accumulation in common forms of Alzheimer’s disease. J. Clin. Invest. 115: 1121.
Garzon-Rodriguez, W., Yatsimirsky, A.K. and Glabe, C.G., 1999, Binding of Zn(II), Cu(II), and Fe(II) ions to Alzheimer’s A beta peptide studied by fluorescence. Bioorg. Med. Chem. Lett. 9: 2243.
Gaskin, F., 1981, In vitro microtubule assembly regulation by divalent cations and nucleotides. Biochemistry 20: 1318.
Gaskin, F. and Kress, Y., 1977, Zinc ion-induced assembly of tubulin. J. Biol. Chem. 252: 6918.
Gaskin, F. and Shelanski, M.L., 1976, Microtubules and intermediate filaments. Essays Biochem. 12: 115.
Geschwind, D.H., 2003, Tau phosphorylation, tangles, and neurodegeneration: the chicken or the egg? Neuron 40: 457.
Gomis-Ruth, F.X., 2003, Structural aspects of the metzincin clan of metalloendopeptidases. Mol. Biotechnol. 24: 157.
Gonzales, P.E., Solomon, A., Miller, A.B., Leesnitzer, M.A., Sagi, I. and Milla, M.E., 2004, Inhibition of the tumor necrosis factor-alpha-converting enzyme by its prodomain. J. Biol. Chem. 279: 31638.
Goode, B.L., Chau, M., Denis, P.E. and Feinstein, S.C., 2000, Structural and functional differences between 3-repeat and 4-repeat tau isoforms. Implications for normal tau function and the onset of neurodegenetative disease. J. Biol. Chem. 275: 38182.
Grundke-Iqbal, I., Fleming, J., Tung, Y.C., Lassmann, H., Iqbal, K. and Joshi, J.G., 1990, Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia. Acta Neuropathol. (Berl) 81: 105.
Gupta, V.B., Anitha, S., Hegde, M.L., Zecca, L.R., Garruto, M., Ravid, R., Shankar, S.K., Stein, R., Shanmugavelu, P. and Jagannatha Rao, K.S., 2005, Aluminium in Alzheimer’s disease: are we still at a crossroad? Cell Mol. Life Sci. 62: 143.
Halliwell, B. and Gutteridge, J.M., 1984, Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219: 1.
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.
Hasan, M.R., Morishima, D., Tomita, K., Katsuki, M. and Kotani, S., 2005, Identification of a 250 kDa putative microtubule-associated protein as bovine ferritin. Evidence for a ferritin-microtubule interaction. FEBS J. 272: 822.
Haydon, P.G., 2001, GLIA: listening and talking to the synapse. Nat. Rev. Neurosci. 2: 185.
Head, E., Garzon-Rodriguez, W., Johnson, J.K., Lott, I.T., Cotman, C.W. and Glabe, C., 2001, Oxidation of Abeta and plaque biogenesis in Alzheimer’s disease and Down syndrome. Neurobiol. Dis. 8: 792.
Heber, S., Herms, J., Gajic, V., Hainfellner, J., Aguzzi, A., Rulicke, T., von Kretzschmar, H., von Koch, C., Sisodia, S., Tremml, P., Lipp, H.P., Wolfer, D.P. and Muller, U., 2000, Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J. Neurosci. 20: 7951.
Hesketh, J.E., 1982, Zinc-stimulated microtubule assembly and evidence for zinc binding to tubulin. Int. J. Biochem. 14: 983.
Hesse, L., Beher, D., Masters, C.L. and Multhaup, G., 1994, The beta A4 amyloid precursor protein binding to copper. FEBS Lett. 349: 109.
Hoke, D.E., Tan, J.L., Ilaya, N.T., Culvenor, J.G., Smith, S.J., White, A.R., Masters, C.L. and Evin, G.M., 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.
Huang, X., Atwood, C.S., Moir, R.D., Hartshorn, M.A., Vonsattel, J.P., Tanzi, R.E. and Bush, A.I., 1997, Zinc-induced Alzheimer’s Abeta1-40 aggregation is mediated by conformational factors. J. Biol. Chem. 272: 26464.
Huang, X., Atwood, C.S., Hartshorn, M.A., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Cuajungco, M.P., Gray, D.N., Lim, J., Moir, R.D., Tanzi, R.E. and Bush, A.I., 1999a, The A beta peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38: 7609.
Huang, X., Cuajungco, M.P., Atwood, C.S., Hartshorn, M.A., Tyndall, J.D., Hanson, G.R., Stokes, K.C., Leopold, M., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Saunders, A.J., Lim, J., Moir, R.D., Glabe, C., Bowden, E.F., Masters, C.L., Fairlie, D.P., Tanzi, R.E. and Bush, A.I., 1999b, Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J. Biol. Chem. 274: 37111.
Huang, X., Atwood, C.S., Moir, R.D., Hartshorn, M.A., Tanzi, R.E. and Bush, A.I., 2004, Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer’s Abeta peptides. J. Biol. Inorg. Chem. 9: 954.
Hyman, B.T., Augustinack, J.C. and Ingelsson, M., 2005, Transcriptional and conformational changes of the tau molecule in Alzheimer’s disease. Biochim. Biophys. Acta 1739: 150.
Inestrosa, N.C., Cerpa, W. and Varela-Nallar, L., 2005, Copper brain homeostasis: role of amyloid precursor protein and prion protein. IUBMB Life 57: 645.
Ischiropoulos, H. and Beckman, J.S., 2003, Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J. Clin. Invest. 111: 163.
Iskra, M., Patelski, J. and Majewski, W., 1993, Concentrations of calcium, magnesium, zinc and copper in relation to free fatty acids and cholesterol in serum of atherosclerotic men. J. Trace Elem. Electrolytes Health Dis. 7: 185.
Iwata, N., Tsubuki, S., Takaki, Y., Watanabe, K., Sekiguchi, M., Hosoki, E., Kawashima-Morishima, M., Lee, H.J., Hama, E., Sekine-Aizawa, Y. and Saido, T.C., 2000, Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat. Med. 6: 143.
Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N.P., Gerard, C., Hama, E., Lee, H.J. and Saido, T.C., 2001, Metabolic regulation of brain Abeta by neprilysin. Science 292: 1550.
Kanemitsu, H., Tomiyama, T. and Mori, H., 2003, Human neprilysin is capable of degrading amyloid beta peptide not only in the monomeric form but also the pathological oligomeric form. Neurosci. Lett. 350: 113.
Karr, J.W., Akintoye, H., Kaupp, L.J. and Szalai, V.A., 2005, N-Terminal deletions modify the Cu2+ binding site in amyloid-beta. Biochemistry 44: 5478.
Ke, Y., Chang, Z., Duan, X.L., Du, J.R., Zhu, L., Wang, K., Yang, X.D., Ho, K.P. and Qian, Z.M., 2005, Age-dependent and iron-independent expression of two mRNA isoforms of divalent metal transporter 1 in rat brain. Neurobiol. Aging 26: 739.
Keen, C.L., Hanna, L.A., Lanoue, L., Uriu-Adams, J.Y., Rucker, R.B. and Clegg, M.S., 2003, Developmental consequences of trace mineral deficiencies in rodents: acute and long-term effects. J. Nutr. 133: 1477S.
Kim, S.U. and de Vellis, J., 2005, Microglia in health and disease. J. Neurosci. Res. 81: 302.
Kim, N.H. and Kang, J.H., 2003, Oxidative modification of neurofilament-L by copper-catalyzed reaction. J. Biochem. Mol. Biol. 36: 488.
Kim, N.H., Jeong, M.S., Choi, S.Y. and Hoon Kang, J., 2004, Oxidative modification of neurofilament-L by the Cu,Zn-superoxide dismutase and hydrogen peroxide system. Biochimie 86: 553.
Klatzo, I., Wisniewski, H. and Streicher, E., 1965, Experimental production of neurofibrillary degeneration. I. Light microscopic observations. J. Neuropathol. Exp. Neurol. 24: 187.
Lammich, S., Kojro, E., Postina, R., Gilbert, S., Pfeiffer, R., Jasionowski, M., Haass, C. and Fahrenholz, F., 1999, Constitutive and regulated alpha-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc. Natl. Acad. Sci. USA 96: 3922.
Lanphear, B.P., Hornung, R., Khoury, J., Yolton, K., Baghurst, P., Bellinger, D.C., Canfield, R.L., Dietrich, K.N., Bornschein, R., Greene, T., Rothenberg, S.J., Needleman, H.L., Schnaas, L., Wasserman, G., Graziano, J. and Roberts, R., 2005, Low-level environmental lead exposure and children’s intellectual function: an international pooled analysis. Environ. Health Perspect. 113: 894.
Lee, J.Y., Cole, T.B., Palmiter, R.D., Suh, S.W. and Koh, J.Y., 2002, Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc. Natl. Acad. Sci. USA 99: 7705.
Lee, J.Y., Friedman, J.E., Angel, I., Kozak, A. and Koh, J.Y., 2004, The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. Neurobiol. Aging 25: 1315.
Leissring, M.A., Farris, W., Chang, A.Y., Walsh, D.M., Wu, X., Sun, X., Frosch, M.P. and Selkoe, D.J., 2003, Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40: 1087.
LeVine, S.M., 1997, Iron deposits in multiple sclerosis and Alzheimer’s disease brains. Brain Res. 760: 298.
Liliom, K., Wagner, G., Kovacs, J., Comin, B., Cascante, M., Orosz, F. and Ovadi, J., 1999, Combined enhancement of microtubule assembly and glucose metabolism in neuronal systems in vitro: decreased sensitivity to copper toxicity. Biochem. Biophys. Res. Commun. 264: 605.
Lind, S.E., McDonagh, J.R. and Smith, C.J., 1993, Oxidative inactivation of plasmin and other serine proteases by copper and ascorbate. Blood 82: 1522.
Lindeman, R.D., Clark, M.L. and Colmore, J.P., 1971, Influence of age and sex on plasma and red-cell zinc concentrations. J. Gerontol. 26: 358.
Ling, Y., Morgan, K. and Kalsheker, N., 2003, Amyloid precursor protein (APP) and the biology of proteolytic processing: relevance to Alzheimer’s disease. Int. J. Biochem. Cell Biol. 35: 1505.
Liu, S.T., Howlett, G. and Barrow, C.J., 1999, Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer’s disease. Biochemistry 38: 9373.
Liu, W.K., Le, T.V., Adamson, J., Baker, M., Cookson, N., Hardy, J., Hutton, M., Yen, S.H. and Dickson, D.W., 2001, Relationship of the extended tau haplotype to tau biochemistry and neuropathology in progressive supranuclear palsy. Ann. Neurol. 50: 494.
Loeffler, D.A., LeWitt, P.A., Juneau, P.L., Sima, A.A., Nguyen, H.U., DeMaggio, A.J., Brickman, C.M., Brewer, G.J., Dick, R.D., Troyer, M.D. and Kanaley, L., 1996, Increased regional brain concentrations of ceruloplasmin in neurodegenerative disorders. Brain Res. 738: 265.
Loske, C., Gerdemann, A., Schepl, W., Wycislo, M., Schinzel, R., Palm, D., Riederer, P. and Munch, G., 2000, Transition metal-mediated glycoxidation accelerates cross-linking of beta-amyloid peptide. Eur. J. Biochem. 267: 4171.
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.
Lovell, M.A., Smith, J.L., Xiong, S. and Markesbery, W.R., 2005, Alterations in zinc transporter protein-1 (ZnT-1) in the brain of subjects with mild cognitive impairment, early, and late-stage Alzheimer’s disease. Neurotox. Res. 7: 265.
Lue, L.F., Kuo, Y.M., Roher, A.E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J.H., Rydel, R.E. and Rogers, J., 1999, Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am. J. Pathol. 155: 853.
Luo, Y., Bolon, B., Kahn, S., Bennett, B.D., Babu-Khan, S., Denis, P., Fan, W., Kha, H., Zhang, J., Gong, Y., Martin, L.J., Louis, C., Yan, Q., Richards, W.G., Citron, M. and Vassar, R., 2001, Mice deficient in BACE1, the Alzheimer’s beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat. Neurosci. 4: 231.
Lutsenko, S. and Petris, M.J., 2003, Function and regulation of the mammalian copper-transporting ATPases: insights from biochemical and cell biological approaches. J. Membr. Biol. 191: 1.
Ma, Q.F., Li, Y.M., Du, J.T., Kanazawa, K., Nemoto, T., Nakanishi, H. and Zhao, Y.F., 2005, Binding of copper (II) ion to an Alzheimer’s tau peptide as revealed by MALDI-TOF MS, CD, and NMR. Biopolymers 79: 74.
Ma, Q., Li, Y., Du, J., Liu, H., Kanazawa, K., Nemoto, T., Nakanishi, H. and Zhao, Y., 2006, Copper binding properties of a tau peptide associated with Alzheimer’s disease studied by CD, NMR, and MALDI-TOF MS. Peptides 27: 841.
Madaric, A., Ginter, E. and Kadrabova, J., 1994, Serum copper, zinc, and copper/zinc ratio in males: influence of aging. Physiol. Res. 43: 107
Mandelkow, E.M., Biernat, J., Drewes, G., Gustke, N., Trinczek, B. and Mandelkow, E., 1995, Tau domains, phosphorylation, and interactions with microtubules. Neurobiol. Aging 16: 355.
Martinez Lista, E., Sole, J., Arola, L. and Mas, A., 1993, Changes in plasma copper and zinc during rat development. Biol. Neonate. 64: 47.
Mattson, M.P., 2004, Pathways toward and away from Alzheimer’s disease. Nature 430: 631.
Maurer, I., Zierz, S. and Moller, H.J., 2000, A selective defect of cytochrome c oxidase is present in brain of Alzheimer’s disease patients. Neurobiol. Aging 21: 455.
Maynard, C.J., Cappai, R., Volitakis, I., Cherny, R.A., White, A.R., Beyreuther, K., Masters, C.L., Bush, A.I. and Li, Q.X., 2002, Overexpression of Alzheimer’s disease amyloid-beta opposes the age-dependent elevations of brain copper and iron. J. Biol. Chem. 277: 44670.
McLean, C.A., Cherny, R.A., Fraser, F.W., Fuller, S.J., Smith, M.J., Beyreuther, K., Bush, A.I. and Masters, C.L., 1999, Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann. Neurol. 46: 860.
McMaster, D., McCrum, E., Patterson, C.C., Kerr, M.M., O'Reilly, D., Evans, A.E. and Love, A.H., 1992, Serum copper and zinc in random samples of the population of Northern Ireland. Am. J. Clin. Nutr. 56: 440.
Mekmouche, Y., Coppel, Y., Hochgrafe, K., Guilloreau, L., Talmard, C., Mazarguil, H. and Faller, P., 2005, Characterization of the ZnII binding to the peptide amyloid-beta1-16 linked to Alzheimer’s disease. Chembiochem 6: 1663.
Menditto, A., Morisi, G., Alimonti, A., Caroli, S., Petrucci F., Spagnolo, A. and Menotti, A., 1993, Association of serum copper and zinc with serum electrolytes and with selected risk factors for cardiovascular disease in men aged 55-75 years. NFR Study Group. J. Trace Elem. Electrolytes Health Dis. 7: 251.
Milne, D.B. and Johnson, P.E., 1993, Assessment of copper status: effect of age and gender on reference ranges in healthy adults. Clin. Chem. 39: 883.
Miura, T., Suzuki, K., Kohata, N. and Takeuchi, H., 2000, Metal binding modes of Alzheimer’s amyloid beta-peptide in insoluble aggregates and soluble complexes. Biochemistry 39: 7024.
Molina, J.A., Jimenez-Jimenez, F.J., Aguilar, M.V., Meseguer, I., Mateos-Vega, C.J., Gonzalez-Munoz, M.J., de Bustos, F., Porta, J., Orti-Pareja, M., Zurdo, M., Barrios, E. and Martinez-Para, M.C., 1998, Cerebrospinal fluid levels of transition metals in patients with Alzheimer’s disease. J. Neural Transm. 105: 479.
Monget, A.L., Galan, P., Preziosi, P., Keller, H., Bourgeois, C., Arnaud, J., Favier, A. and Hercberg, S., 1996, Micronutrient status in elderly people. Geriatrie/Min. Vit. Aux Network. Int. J. Vitam. Nutr. Res. 66: 71.
Moreira, P.I., Siedlak, S.L., Aliev, G., Zhu, X., Cash, A.D., Smith, M.A. and Perry, G., 2005, Oxidative stress mechanisms and potential therapeutics in Alzheimer’s disease. J. Neural Transm. 112: 921.
Morris, C.M., Kerwin, J.M. and Edwardson, J.A., 1994, Nonhaem iron histochemistry of the normal and Alzheimer’s disease hippocampus. Neurodegeneration 3: 267.
Moskovitz, J., Bar-Noy, S., Williams, W.M., Requena, J., Berlett, B.S. and Stadtman, E.R., 2001, Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. Proc. Natl. Acad. Sci. USA 98: 12920.
Mrak, R.E. and Griffin, S.W., 2005, Glia and their cytokines in progression of neurodegeneration. Neurobiol. Aging 26: 349.
Muller, U., Cristina, N., Li, Z.W., Wolfer, D.P., Lipp, H.P., Rulicke, T., Brandner, S., Aguzzi, A. and Weissmann, C., 1994, Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. Cell 79: 755.
Multhaup, G., Bush, A.I., Pollwein, P. and Masters, C.L., 1994, Interaction between the zinc (II) and the heparin binding site of the Alzheimer’s disease beta A4 amyloid precursor protein (APP). FEBS Lett. 355: 151.
Multhaup, G., Schlicksupp, A., Hesse, L., Beher, D., Ruppert, T., Masters, C.L. and Beyreuther, K., 1996, The amyloid precursor protein of Alzheimer’s disease in the reduction of copper(II) to copper(I). Science 271: 1406.
Munoz, D.G., 1998, Is exposure to aluminum a risk factor for the development of Alzheimer disease? - No. Arch. Neurol. 55: 737.
Munro, H.N., Suter, P.M. and Russell, R.M., 1987, Nutritional requirements of the elderly. Annu. Rev. Nutr. 7: 23.
Nagele, R.G., D’Andrea, M.R., Lee, H., Venkataraman, V. and Wang, H.Y., 2003, Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer’s disease brains. Brain Res. 971: 197.
Nagele, R.G., Wegiel, J., Venkataraman, V., Imaki, H. and Wang, K.C., 2004, Contribution of glial cells to the development of amyloid plaques in Alzheimer’s disease. Neurobiol. Aging 25: 663.
Omar, R.A., Chyan, Y.J., Andorn, A.C., Poeggeler, B., Robakis, N.K. and Pappolla, M.A., 1999, Increased expression but reduced activity of antioxidant enzymes in Alzheimer’s disease. J. Alzheimers Dis. 1: 139.
Opazo, C., Ruiz, F.H. and Inestrosa, N.C., 2000, Amyloid-beta-peptide reduces copper(II) to copper(I) independent of its aggregation state. Biol. Res. 33: 125.
Opazo, C., Huang, X., Cherny, R.A., Moir, R.D., Roher, A.E., White, A.R., Cappai, R., Masters, C.L., Tanzi, R.E., Inestrosa, N.C. and Bush, A.I., 2002, Metalloenzyme-like activity of Alzheimer’s disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2. J. Biol. Chem. 277: 40302.
Opazo, C., Luza, S., Villemagne, V.L., Volitakis, I., Rowe, C., Barnham, K.J., Strozyk, D., Masters, C.L., Cherny, R.A. and Bush, A.I., 2006, Radioiodinated clioquinol as a biomarker for ß-amyloid:Zn2+ complexes in Alzheimer’s disease. Aging Cell 5: 69.
Oteiza, P.I., Cuellar, S., Lonnerdal, B., Hurley, L.S. and Keen, C.L., 1990a, Influence of maternal dietary zinc intake on in vitro tubulin polymerization in fetal rat brain. Teratology 41: 97.
Oteiza, P.I., Hurley, L.S., Lonnerdal, B. and Keen, C.L., 1990b, Effects of marginal zinc deficiency on microtubule polymerization in the developing rat brain. Biol. Trace Elem. Res. 24: 13.
Pappolla, M.A., Omar, R.A., Kim, K.S. and Robakis, N.K., 1992, Immunohistochemical evidence of oxidative (corrected) stress in Alzheimer’s disease. Am. J. Pathol. 140: 621.
Park, I.H., Jung, M.W., Mori, H. and Mook-Jung, I., 2001, Zinc enhances synthesis of presenilin 1 in mouse primary cortical culture. Biochem. Biophys Res. Commun. 285: 680.
Perez, M., Valpuesta, J.M., de Garcini, E.M., Quintana, C., Arrasate, M., Lopez Carrascosa, J.L., Rabano, A., Garcia de Yebenes, J. and Avila, J., 1998, Ferritin is associated with the aberrant tau filaments present in progressive supranuclear palsy. Am. J. Pathol. 152: 1531.
Perry, G., Cash, A.D. and Smith, M.A., 2002, Alzheimer’s disease and oxidative stress. J. Biomed. Biotechnol. 2: 120.
Petersen, R.C., 2004, Mild cognitive impairment as a diagnostic entity. J. Intern. Med. 256: 183.
Petersen, R.C., Smith, G.E., Waring, S.C., Ivnik, R.J., Tangalos, E.G. and Kokmen, E., 1999, Mild cognitive impairment: clinical characterization and outcome. Arch. Neurol. 56: 303.
Phinney, A.L., Drisaldi, B., Schmidt, S.D., Lugowski, S., Coronado, V., Liang, Y., Horne, P., Yang, J., Sekoulidis, J., Coomaraswamy, J., Chishti, M.A., Cox, D.W., Mathews, P.M., Nixon, R.A., Carlson, G.A., St GeorgeHyslop, P. and Westaway, D., 2003, In vivo reduction of amyloid-beta by a mutant copper transporter. Proc. Natl. Acad. Sci. USA 100: 14193.
Pierson, K.B. and Evenson, M.A., 1988, Kd neurofilament protein binds Al, Cu, and Zn. Biochem. Biophys. Res. Commun. 152: 598.
Plantin, L.-O., Lysing-Tunnell, U. and Kristensson, K., 1987, Trace elements in the human central nervous system studied with neutron activation analysis. Biol. Trace Elem. Res. 13: 69.
Prasad, A.S., Fitzgerald, J.T., Hess, J.W., Kaplan, J., Pelen, F. and Dardenne, M., 1993, Zinc deficiency in elderly patients. Nutrition 9: 218.
Prohaska, J.R. and Gybina, A.A., 2004, Intracellular copper transport in mammals. J. Nutr. 134: 1003.
Puglielli, L., Friedlich, A.L., Setchell, K.D., Nagano, S., Opazo, C., Cherny, R.A., Barnham, K.J., Wade, J.D., Melov, S., Kovacs, D.M. and Bush, A.I., 2005, Alzheimer disease beta-amyloid activity mimics cholesterol oxidase. J. Clin. Invest. 115: 2556.
Quinta-Ferreira, M.E. and Matias, C.M., 2005, Tetanically released zinc inhibits hippocampal mossy fiber calcium, zinc, and synaptic responses. Brain Res. 1047: 1.
Rae, T.D., Schmidt, P.J., Pufahl, R.A., Culotta, V.C. and O’Halloran, T.V., 1999, Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. Science 284: 805.
Rajan, M.T., Jagannatha Rao, K.S., Mamatha, B.M., Rao, R.V., Shanmugavelu, P., Menon, R.B. and Pavithran, M.V., 1997, Quantification of trace elements in normal human brain by inductively coupled plasma atomic emission spectrometry. J. Neurol. Sci. 146: 153.
Raman, B., Ban, T., Yamaguchi, K., Sakai, M., Kawai, T., Naiki, H. and Goto, Y., 2005, Metal ion-dependent effects of clioquinol on the fibril growth of an amyloid-beta peptide. J. Biol. Chem. 280: 16157.
Rao, K.S.J., Rao, R.V., Shanmugavelu, P. and Menon, R.B., 1999, Trace elements in Alzheimer’s disease brain: A new hypothesis. Alzheimers Rep. 241.
Ravaglia, G., Forti, P., Maioli, F., Nesi, B., Pratelli, L., Savarino, L., Cucinotta, D. and Cavalli, G., 2000, Blood micronutrient and thyroid hormone concentrations in the oldest-old. J. Clin. Endocrinol. Metab. 85: 2260.
Reinhard, C., Hebert, S.S. and De Strooper, B., 2005, The amyloid-beta precursor protein: integrating structure with biological function. EMBO J. 24: 3996.
Ritchie, C.W., Bush, A.I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., Kiers, L., Cherny, R., Li, Q.X., Tammer, A., Carrington, D., Mavros, C., Volitakis, I., Xilinas, I.M., Ames, D., Davis, S., Beyreuther, K., Tanzi, R.E. and Masters, C.L., 2003, Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer’s disease: a pilot phase 2 clinical trial. Arch. Neurol 60: 1685.
Rogers, J.T., Randall, J.D., Cahill, C.M., Eder, P.S., Huang, X., Gunshin, H., Leiter, L., McPhee, J., Sarang, S.S., Utsuki, T., Greig, N.H., Lahiri, D.K., Tanzi, R.E., Bush, A.I., Giordano, T. and Gullans, S.R., 2002, An iron-responsive element type II in the 5′-untranslated region of the Alzheimer’s amyloid precursor protein transcript. J. Biol. Chem. 277: 45518.
Rosenberg, P.B., 2005, Clinical aspects of inflammation in Alzheimer’s disease. Int. Rev. Psychiatry 17: 503.
Rottkamp, C.A., Raina, A.K., Zhu, X., Gaier, E., Bush, A.I., Atwood, C.S., Chevion, M., Perry, G. and Smith, M.A., 2001, Redox-active iron mediates amyloid-beta toxicity. Free. Radic. Biol. Med. 30: 447.
Ruiz, F.H., Gonzalez, M., Bodini, M., Opazo, C. and Inestrosa, N.C., 1999, Cysteine 144 is a key residue in the copper reduction by the beta-amyloid precursor protein. J. Neurochem. 73: 1288.
Sagara, Y., Dargusch, R., Klier, F.G., Schubert, D. and Behl, C., 1996, Increased antioxidant enzyme activity in amyloid beta protein-resistant cells. J. Neurosci. 16: 497.
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.
Scheuermann, S., Hambsch, B., Hesse, L., Stumm, J., Schmidt, C., Beher, D., Bayer, T.A., Beyreuther, K. and Multhaup, G., 2001, Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer’s disease. J. Biol. Chem. 276: 33923.
Schlief, M.L., Craig, A.M. and Gitlin, J.D., 2005, NMDA receptor activation mediates copper homeostasis in hippocampal neurons. J. Neurosci. 25: 239.
Schonheit, B., Zarski, R. and Ohm, T.G., 2004, Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol. Aging 25: 697.
Schubert, D. and Chevion, M., 1995, The role of iron in beta amyloid toxicity. Biochem. Biophys. Res. Commun. 216: 702.
Schuessel, K., Schafer, S., Bayer, T.A., Czech, C., Pradier, L., Muller-Spahn, F., Muller, W.E. and Eckert, A., 2005, Impaired Cu/Zn-SOD activity contributes to increased oxidative damage in APP transgenic mice. Neurobiol. Dis. 18: 89.
Selley, M.L., Close, D.R. and Stern, S.E., 2002, The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer’s disease. Neurobiol. Aging 23: 383.
Serrano, L., Dominguez, J.E. and Avila, J., 1988, Identification of zinc-binding sites of proteins: zinc binds to the amino-terminal region of tubulin. Anal. Biochem. 172: 210.
Shinall, H., Song, E.S. and Hersh, L.B., 2005, Susceptibility of amyloid ß peptide degrading enzymes to oxidative damage: a potential Alzheimer’s disease spiral. Biochemistry 44: 15345.
Shivers, B.D., Hilbich, C., Multhaup, G., Salbaum, M., Beyreuther, K. and Seeburg, P.H., 1988, Alzheimer’s disease amyloidogenic glycoprotein: expression pattern in rat brain suggests a role in cell contact. EMBO J. 7: 1365.
Simons, A., Ruppert, T., Schmidt, C., Schlicksupp, A., Pipkorn, R., Reed, J., Masters, C.L., White, A.R., Cappai, R., Beyreuther, K., Bayer, T.A. and Multhaup, G., 2002, Evidence for a copper-binding superfamily of the amyloid precursor protein. Biochemistry 41: 9310.
Sinha, S., Anderson, J.P., Barbour, R., Basi, G.S., Caccavello, R., Davis, D., Doan, M., Dovey, H.F., Frigon, N., Hong, J., Jacobson-Croak, K., Jewett, N., Keim, P., Knops, J., Lieberburg, I., Power, M., Tan, H., Tatsuno, G., Tung, J., Schenk, D., Seubert, P., Suomensaari, S.M., Wang, S., Walker, D., Zhao, J., McConlogue, L. and John, V., 1999, Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 402: 537.
Smith, M.A., Wehr, K., Harris, P.L., Siedlak, S.L., Connor, J.R. and Perry, G., 1998, Abnormal localization of iron regulatory protein in Alzheimer’s disease. Brain Res. 788: 232.
Sparks, D.L. and Schreurs, B.G., 2003, Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 100: 11065.
Squier, T.C., 2001, Oxidative stress and protein aggregation during biological aging. Exp. Gerontol. 36: 1539.
Squitti, R., Lupoi, D., Pasqualetti, P., Dal Forno, G., Vernieri, F., Chiovenda, P., Rossi, L., Cortesi, M., Cassetta, E. and Rossini, P.M., 2002, Elevation of serum copper levels in Alzheimer’s disease. Neurology 59: 1153.
Squitti, R., Cassetta, E., Dal Forno, G., Lupoi, D., Lippolis, G., Pauri, F., Vernieri, F., Cappa, A. and Rossini, P.M., 2004, Copper perturbation in 2 monozygotic twins discordant for degree of cognitive impairment. Arch. Neurol. 61: 738.
Streit, W.J., 2004, Microglia and Alzheimer’s disease pathogenesis. J. Neurosci. Res. 77: 1.
Suh, S.W., Jensen, K.B., Jensen, M.S., Silva, D.S., Kesslak, P.J., Danscher, G. and Frederickson, C.J., 2000, Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer’s diseased brains. Brain Res. 852: 274.
Suh, Y.H. and Checler, F., 2002, Amyloid precursor protein, presenilins, and alpha-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer’s disease. Pharmacol. Rev. 54: 469.
Sullivan, P.G. and Brown, M.R., 2005, Mitochondrial aging and dysfunction in Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 29: 407.
Syme, C.D., Nadal, R.C., Rigby, S.E. and Viles, J.H., 2004, Copper binding to the amyloid-beta (Abeta) peptide associated with Alzheimer’s disease: folding, coordination geometry, pH dependence, stoichiometry, and affinity of Abeta-(1-28): insights from a range of complementary spectroscopic techniques. J. Biol. Chem. 279: 18169.
Tanzi, R.E. and Bertram, L., 2005, Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell 120: 545.
Tarohda, T., Yamamoto, M. and Amamo, R., 2004, Regional distribution of manganese, iron, copper, and zinc in the rat brain during development. Anal. Bioanal. Chem. 380: 240.
Terry, R.D., 1996, The pathogenesis of Alzheimer’s disease: an alternative to the amyloid hypothesis. J. Neuropathol. Exp. Neurol. 55: 1023.
Terry, R.D. and Wisniewski, H.M., 1975, Structural and chemical changes of the aged human brain. Psychopharmacol. Bull. 11: 46.
Treiber, C., Simons, A., Strauss, M., Hafner, M., Cappai, R., Bayer, T.A. and Multhaup, G., 2004, Clioquinol mediates copper uptake and counteracts copper efflux activities of the amyloid precursor protein of Alzheimer’s disease. J. Biol. Chem. 279: 51958.
Uchida, Y., Takio, K., Titani, K., Ihara, Y. and Tomonaga, M., 1991, The growth inhibitory factor that is deficient in the Alzheimer’s disease brain is a 68 amino acid metallothionein-like protein. Neuron 7: 337.
Valensin, D.F., Mancini, M., Luczkowski, M., Janicka, A., Wisniewska, K., Gaggelli, E., Valensin, G., Lankiewicz, L. and Kozlowski, H., 2004, Identification of a novel high affinity copper binding site in the APP(145-155) fragment of amyloid precursor protein. Dalton Trans. 1: 16.
Valko, M., Morris, H. and Cronin, M.T., 2005, Metals, toxicity, and oxidative stress. Curr. Med. Chem. 12: 1161.
Vassar, R., Bennett, B.D., Babu-Khan, S., Kahn, S., Mendiaz, E.A., Denis, P., Teplow, D.B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., Lile, J., Jarosinski, M.A., Biere, A.L., Curran, E., Burgess, T., Louis, J.C., Collins, F., Treanor, J., Rogers, G. and Citron, M., 1999, Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286: 735.
Venti, A., Giordano, T., Eder, P., Bush, A.I., Lahiri, D.K., Greig, N.H. and Rogers, J.T., 2004, The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5′-untranslated region. Ann. NY Acad. Sci. 1035: 34.
Vickers, J.C., Dickson, T.C., Adlard, P.A., Saunders, H.L., King, C.E. and McCormack, G., 2000, The cause of neuronal degeneration in Alzheimer’s disease. Prog. Neurobiol. 60: 139.
Walsh, J.S., Welch, H.G. and Larson, E.B., 1990, Survival of outpatients with Alzheimer-type dementia. Ann. Intern. Med. 113: 429.
Walsh, D.M., Klyubin, I., Fadeeva, J.V., Cullen, W.K., Anwyl, R., Wolfe, M.S., Rowan, M.J. and Selkoe, D.J., 2002a, Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535.
Walsh, D.M., Klyubin, I., Fadeeva, J.V., Rowan, M.J. and Selkoe, D.J., 2002b, Amyloid-beta oligomers: their production, toxicity, and therapeutic inhibition. Biochem. Soc. Trans. 30: 552.
Wang, J., Dickson, D.W., Trojanowski, J.Q. and Lee, V.M., 1999, The levels of soluble versus insoluble brain Abeta distinguish Alzheimer’s disease from normal and pathologic aging. Exp. Neurol. 158: 328.
Wang, D.S., Iwata, N., Hama, E., Saido, T.C. and Dickson, D.W., 2003, Oxidized neprilysin in aging and Alzheimer’s disease brains. Biochem. Biophys Res. Commun. 310: 236.
Wang, Q., Woltjer, R.L., Cimino, P.J., Pan, C., Montine, K.S., Zhang, J. and Montine, T.J., 2005, Proteomic analysis of neurofibrillary tangles in Alzheimer’s disease identifies GAPDH as a detergent-insoluble paired helical filament tau binding protein. FASEB J. 19: 869.
Weisenberg, R.C., 1972, Microtubule formation in vitro in solutions containing low calcium concentrations. Science 177: 1104.
Weisskopf, M.G., Wright, R.O., Schwartz, J., Spiro, A. 3rd, Sparrow, D., Aro, A. and Hu, H., 2004, Cumulative lead exposure and prospective change in cognition among elderly men: the VA normative aging study. Am. J. Epidemiol. 160: 1184.
Wender, M., Szczech, J., Hoffmann, S. and Hilczer, W., 1992, Electron paramagnetic resonance analysis of heavy metals in the aging human brain. Neuropatol. Pol. 30: 65.
White, A.R., Reyes, R., Mercer, J.F., Camakaris, J., Zheng, H., Bush, A.I., Multhaup, G., Beyreuther, K., Masters, C.L. and Cappai, R., 1999, Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res. 842: 439.
Wille, H., Drewes, G., Biernat, J., Mandelkow, E.M. and Mandelkow, E., 1992, Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro. J. Cell Biol. 118: 573.
Wojtera, M., Sikorska, B., Sobow, T. and Liberski, P.P., 2005, Microglial cells in neurodegenerative disorders. Folia Neuropathol. 43: 311.
Yamamoto, A., Shin, R.W., Hasegawa, K., Naiki, H., Sato, H., Yoshimasu, F. and Kitamoto, T., 2002, Iron (III) induces aggregation of hyperphosphorylated tau and its reduction to iron (II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer’s disease. J. Neurochem. 82: 1137.
Yan, R., Bienkowski, M.J., Shuck, M.E., Miao, H., Tory, M.C., Pauley, A.M., Brashier, J.R., Stratman, N.C., Mathews, W.R., Buhl, A.E., Carter, D.B., Tomasselli, A.G., Parodi, L.A., Heinrikson, R.L. and Gurney, M.E., 1999, Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity. Nature 402: 533.
Yang, D.S., McLaurin, J., Qin, K., Westaway, D. and Fraser, P.E., 2000, Examining the zinc binding site of the amyloid-beta peptide. Eur. J. Biochem. 267: 6692.
Yong, V.W., Krekoski, C.A., Forsyth, P.A., Bell, R. and Edwards, D.R., 1998, Matrix metalloproteinases and diseases of the CNS. Trends Neurosci. 21: 75.
Yoshiike, Y., Tanemura, K., Murayama, O., Akagi, T., Murayama, M., Sato, S., Sun, X., Tanaka, N. and Takashima, A., 2001, New insights on how metals disrupt amyloid beta-aggregation and their effects on amyloid-beta cytotoxicity. J. Biol. Chem. 276: 32293.
Yu, W.H., Lukiw, W.J., Bergeron, C., Niznik, H.B. and Fraser, P.E., 2001, Metallothionein III is reduced in Alzheimer’s disease. Brain Res. 894: 37.
Zemlan, F.P., Thienhaus, O.J. and Bosmann, H.B., 1989, Superoxide dismutase activity in Alzheimer’s disease: possible mechanism for paired helical filament formation. Brain Res. 476: 160.
Zhao, G., Cui, M.Z., Mao, G., Dong, Y., Tan, J., Sun, L. and Xu, X., 2005, Gamma-cleavage is dependent on zeta-cleavage during the proteolytic processing of amyloid precursor protein within its transmembrane domain. J. Biol. Chem. 280: 37689.
Zheng, H., Jiang, M., Trumbauer, M.E., Sirinathsinghji, D.J., Hopkins, R., Smith, D.W., Heavens, R.P., Dawson, G.R., Boyce, S., Conner, M.W., Stevens, K.A., Slunt, H.H., Sisoda, S.S., Chen, H.Y. and Van der Ploeg, L.H., 1995, Abeta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81: 525.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Adlard, P.A., Bush, A.I. (2007). Metal Ions and Alzheimer's Disease. In: Malva, J.O., Rego, A.C., Cunha, R.A., Oliveira, C.R. (eds) Interaction Between Neurons and Glia in Aging and Disease. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-70830-0_15
Download citation
DOI: https://doi.org/10.1007/978-0-387-70830-0_15
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-70829-4
Online ISBN: 978-0-387-70830-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)