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International Journal of Alzheimer’s Disease
Volume 2013, Article ID 145345, 12 pages
http://dx.doi.org/10.1155/2013/145345
Review Article

Neuroinflammation and Copper in Alzheimer’s Disease

Department of Pathology, University of Melbourne, VIC 3010, Australia

Received 19 August 2013; Accepted 22 October 2013

Academic Editor: Renato Polimanti

Copyright © 2013 Xin Yi Choo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. Newton and V. M. Dixit, “Signaling in innate immunity and inflammation,” Cold Spring Harbor Perspectives in Biology, vol. 4, no. 3, Article ID a006049, 2012. View at Google Scholar
  2. J. R. Murdoch and C. M. Lloyd, “Chronic inflammation and asthma,” Mutation Research, vol. 690, no. 1-2, pp. 24–39, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Xu, G. T. Barnes, Q. Yang et al., “Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1821–1830, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. J. Danesh, P. Whincup, M. Walker et al., “Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses,” British Medical Journal, vol. 321, no. 7255, pp. 199–204, 2000. View at Google Scholar · View at Scopus
  5. M. Fillon, “Details linking chronic inflammation and cancer continue to emerge,” Journal of the National Cancer Institute, vol. 105, no. 8, pp. 509–510, 2013. View at Publisher · View at Google Scholar
  6. L. Minghetti, “Role of inflammation in neurodegenerative diseases,” Current Opinion in Neurology, vol. 18, no. 3, pp. 315–321, 2005. View at Google Scholar · View at Scopus
  7. T. Wyss-Coray and L. Mucke, “Inflammation in neurodegenerative disease-a double-edged sword,” Neuron, vol. 35, no. 3, pp. 419–432, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. J. K. Krishnaswamy, T. Chu, and S. C. Eisenbarth, “Beyond pattern recognition: NOD-like receptors in dendritic cells,” Trends in Immunology, vol. 34, no. 5, pp. 224–233, 2013. View at Publisher · View at Google Scholar
  9. K. Takeda and S. Akira, “TLR signaling pathways,” Seminars in Immunology, vol. 16, no. 1, pp. 3–9, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. L. A. O'Neill and A. G. Bowie, “The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling,” Nature Reviews Immunology, vol. 7, no. 5, pp. 353–364, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. R. Medzhitov, “Toll-like receptors and innate immunity,” Nature Reviews Immunology, vol. 1, no. 2, pp. 135–145, 2001. View at Google Scholar · View at Scopus
  12. T. H. Mogensen, “Pathogen recognition and inflammatory signaling in innate immune defenses,” Clinical Microbiology Reviews, vol. 22, no. 2, pp. 240–273, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. C. Becker and L. A. J. O'Neill, “Inflammasomes in inflammatory disorders: the role of TLRs and their interactions with NLRs,” Seminars in Immunopathology, vol. 29, no. 3, pp. 239–248, 2007. View at Publisher · View at Google Scholar · View at Scopus
  14. P. P. Tak and G. S. Firestein, “NF-κB: a key role in inflammatory diseases,” Journal of Clinical Investigation, vol. 107, no. 1, pp. 7–11, 2001. View at Google Scholar · View at Scopus
  15. R. J. Kelly, A. M. Minogue, A. Lyons et al., “Glial activation in AbetaPP/PS1 mice is associated with infiltration of IFNgamma-producing cells,” Journal of Alzheimer's Disease, vol. 37, no. 1, pp. 63–75, 2013. View at Google Scholar
  16. O. Takeuchi and S. Akira, “Pattern recognition receptors and inflammation,” Cell, vol. 140, no. 6, pp. 805–820, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Proell, S. J. Riedl, J. H. Fritz, A. M. Rojas, and R. Schwarzenbacher, “The Nod-Like Receptor (NLR) family: a tale of similarities and differences,” PLoS ONE, vol. 3, no. 4, Article ID e2119, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. P. J. Shaw, M. Lamkanfi, and T. Kanneganti, “NOD-like receptor (NLR) signaling beyond the inflammasome,” European Journal of Immunology, vol. 40, no. 3, pp. 624–627, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. T. A. Kufer, “Signal transduction pathways used by NLR-type innate immune receptors,” Molecular BioSystems, vol. 4, no. 5, pp. 380–386, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. P. Duewell, H. Kono, K. J. Rayner et al., “NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals,” Nature, vol. 464, no. 7293, pp. 1357–1361, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. S. C. Eisenbarth, O. R. Colegio, W. O'Connor Jr., F. S. Sutterwala, and R. A. Flavell, “Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants,” Nature, vol. 453, no. 7198, pp. 1122–1126, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. F. Martinon, V. Pétrilli, A. Mayor, A. Tardivel, and J. Tschopp, “Gout-associated uric acid crystals activate the NALP3 inflammasome,” Nature, vol. 440, no. 7081, pp. 237–241, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. S. L. Masters and L. A. J. O'Neill, “Disease-associated amyloid and misfolded protein aggregates activate the inflammasome,” Trends in Molecular Medicine, vol. 17, no. 5, pp. 276–282, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. W. S. Griffin, J. G. Sheng, M. C. Royston et al., “Glial-neuronal interactions in Alzheimer's disease: the potential role of a 'cytokine cycle' in disease progression,” Brain Pathology, vol. 8, no. 1, pp. 65–72, 1998. View at Google Scholar · View at Scopus
  25. H. Ogura, M. Murakami, Y. Okuyama et al., “Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction,” Immunity, vol. 29, no. 4, pp. 628–636, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Hanada and A. Yoshimura, “Regulation of cytokine signaling and inflammation,” Cytokine and Growth Factor Reviews, vol. 13, no. 4-5, pp. 413–421, 2002. View at Publisher · View at Google Scholar · View at Scopus
  27. Z. Zheng, C. White, J. Lee et al., “Altered microglial copper homeostasis in a mouse model of Alzheimer's disease,” Journal of Neurochemistry, vol. 114, no. 6, pp. 1630–1638, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. K. H. Lee, S. Yun, K. N. Nam, Y. S. Gho, and E. H. Lee, “Activation of microglial cells by ceruloplasmin,” Brain Research, vol. 1171, no. 1, pp. 1–8, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. A. Becaria, D. K. Lahiri, S. C. Bondy et al., “Aluminum and copper in drinking water enhance inflammatory or oxidative events specifically in the brain,” Journal of Neuroimmunology, vol. 176, no. 1-2, pp. 16–23, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Lu, D. Wu, Y. Zheng et al., “Trace amounts of copper exacerbate beta amyloid-induced neurotoxicity in the cholesterol-fed mice through TNF-mediated inflammatory pathway,” Brain, Behavior, and Immunity, vol. 23, no. 2, pp. 193–203, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Rossi-George, C.-J. Guo, B. L. Oakes, and A. J. Gow, “Copper modulates the phenotypic response of activated BV2 microglia through the release of nitric oxide,” Nitric Oxide, vol. 27, no. 4, pp. 201–209, 2012. View at Publisher · View at Google Scholar
  32. C. J. Maynard, R. Cappai, I. Volitakis et al., “Overexpression of Alzheimer's disease amyloid-β opposes the age-dependent elevations of brain copper and iron,” Journal of Biological Chemistry, vol. 277, no. 47, pp. 44670–44676, 2002. View at Publisher · View at Google Scholar · View at Scopus
  33. S. A. Bellingham, D. K. Lahiri, B. Maloney, S. La Fontaine, G. Multhaup, and J. Camakaris, “Copper depletion down-regulates expression of the Alzheimer's disease amyloid-β precursor protein gene,” Journal of Biological Chemistry, vol. 279, no. 19, pp. 20378–20386, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. S. L. Bailey, P. A. Carpentier, E. J. McMahon, W. S. Begolka, and S. D. Miller, “Innate and adaptive immune responses of the central nervous system,” Critical Reviews Immunology, vol. 26, no. 2, pp. 149–188, 2006. View at Publisher · View at Google Scholar
  35. J. J. Bajramovic, “Regulation of innate immune responses in the central nervous system,” CNS & Neurological Disorders Drug Targets, vol. 10, no. 1, pp. 4–24, 2011. View at Google Scholar · View at Scopus
  36. R. O. Weller, E. Djuanda, H. Yow, and R. O. Carare, “Lymphatic drainage of the brain and the pathophysiology of neurological disease,” Acta Neuropathologica, vol. 117, no. 1, pp. 1–14, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. B.-G. Xiao and H. Link, “Immune regulation within the central nervous system,” Journal of the Neurological Sciences, vol. 157, no. 1, pp. 1–12, 1998. View at Publisher · View at Google Scholar · View at Scopus
  38. P. Kivisäkk, D. J. Mahad, M. K. Callahan et al., “Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 14, pp. 8389–8394, 2003. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Kida, R. O. Weller, E.-T. Zhang, M. J. Phillips, and F. Iannotti, “Anatomical pathways for lymphatic drainage of the brain and their pathological significance,” Neuropathology and Applied Neurobiology, vol. 21, no. 3, pp. 181–184, 1995. View at Google Scholar · View at Scopus
  40. C. K. Glass, K. Saijo, B. Winner, M. C. Marchetto, and F. H. Gage, “Mechanisms underlying inflammation in neurodegeneration,” Cell, vol. 140, no. 6, pp. 918–934, 2010. View at Publisher · View at Google Scholar · View at Scopus
  41. W. J. Streit, R. E. Mrak, and W. S. T. Griffin, “Microglia and neuroinflammation: a pathological perspective,” Journal of Neuroinflammation, vol. 1, no. 1, p. 14, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. M. E. Alexianu, M. Kozovska, and S. H. Appel, “Immune reactivity in a mouse model of familial ALS correlates with disease progression,” Neurology, vol. 57, no. 7, pp. 1282–1289, 2001. View at Google Scholar · View at Scopus
  43. T. Autti, R. Raininko, P. Santavuori, S. L. Vanhanen, V. P. Poutanen, and M. Haltia, “MRI of neuronal ceroid lipofuscinosis. II. Postmortem MRI and histopathological study of the brain in 16 cases of neuronal ceroid lipofuscinosis of juvenile or late infantile type,” Neuroradiology, vol. 39, no. 5, pp. 371–377, 1997. View at Publisher · View at Google Scholar · View at Scopus
  44. M. E. Bamberger, M. E. Harris, D. R. McDonald, J. Husemann, and G. E. Landreth, “A cell surface receptor complex for fibrillar β-amyloid mediates microglial activation,” Journal of Neuroscience, vol. 23, no. 7, pp. 2665–2674, 2003. View at Google Scholar · View at Scopus
  45. P. Damier, E. C. Hirsch, P. Zhang, Y. Agid, and F. Javoy-Agid, “Glutathione peroxidase, glial cells and Parkinson's disease,” Neuroscience, vol. 52, no. 1, pp. 1–6, 1993. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Ingelsson, H. Fukumoto, K. L. Newell et al., “Early Aβ accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain,” Neurology, vol. 62, no. 6, pp. 925–931, 2004. View at Google Scholar · View at Scopus
  47. H. Kamo, H. Haebara, and I. Akiguchi, “A distinctive distribution of reactive astroglia in the precentral cortex in amyotrophic lateral sclerosis,” Acta Neuropathologica, vol. 74, no. 1, pp. 33–38, 1987. View at Google Scholar · View at Scopus
  48. S. Thellung, T. Florio, A. Corsaro et al., “Intracellular mechanisms mediating the neuronal death and astrogliosis induced by the prion protein fragment 106-126,” International Journal of Developmental Neuroscience, vol. 18, no. 4-5, pp. 481–492, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. D. W. Dickson, J. Farlo, P. Davies, H. Crystal, P. Fuld, and S.-H. C. Yen, “Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques,” American Journal of Pathology, vol. 132, no. 1, pp. 86–101, 1988. View at Google Scholar · View at Scopus
  50. P. L. McGeer, H. Akiyama, S. Itagaki, and E. G. McGeer, “Immune system response in Alzheimer's disease,” Canadian Journal of Neurological Sciences, vol. 16, supplement 4, pp. 516–527, 1989. View at Google Scholar · View at Scopus
  51. J. M. Rozemuller, P. Eikelenboom, S. T. Pals, and F. C. Stam, “Microglial cells around amyloid plaques in Alzheimer's disease express leucocyte adhesion molecules of the LFA-1 family,” Neuroscience Letters, vol. 101, no. 3, pp. 288–292, 1989. View at Google Scholar · View at Scopus
  52. K. Jomova, D. Vondrakova, M. Lawson, and M. Valko, “Metals, oxidative stress and neurodegenerative disorders,” Molecular and Cellular Biochemistry, vol. 345, no. 1-2, pp. 91–104, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. M. Valko, H. Morris, and M. T. D. Cronin, “Metals, toxicity and oxidative stress,” Current Medicinal Chemistry, vol. 12, no. 10, pp. 1161–1208, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. K. T. Akama, C. Albanese, R. G. Pestell, and L. J. Van Eldik, “Amyloid β-peptide stimulates nitric oxide production in astrocytes through an NFκb-dependent mechanism,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 10, pp. 5795–5800, 1998. View at Publisher · View at Google Scholar · View at Scopus
  55. K. C. Flanders, C. F. Lippa, T. W. Smith, D. A. Pollen, and M. B. Sporn, “Altered expression of transforming growth factor-β in Alzheimer's disease,” Neurology, vol. 45, no. 8, pp. 1561–1569, 1995. View at Google Scholar · View at Scopus
  56. P. Grammas and R. Ovase, “Inflammatory factors are elevated in brain microvessels in Alzheimer's disease,” Neurobiology of Aging, vol. 22, no. 6, pp. 837–842, 2001. View at Publisher · View at Google Scholar · View at Scopus
  57. L. F. Lue, R. Rydel, E. F. Brigham et al., “Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro,” Glia, vol. 35, no. 1, pp. 72–79, 2001. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Akiyama, W. Streit, R. Strohmeyer et al., “Inflammation and Alzheimer's disease,” Neurobiology of Aging, vol. 21, no. 3, pp. 383–421, 2000. View at Publisher · View at Google Scholar
  59. A. Salminen, J. Ojala, A. Kauppinen, K. Kaarniranta, and T. Suuronen, “Inflammation in Alzheimer's disease: amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors,” Progress in Neurobiology, vol. 87, no. 3, pp. 181–194, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. E. Mocchegiani, L. Costarelli, R. Giacconi, F. Piacenza, A. Basso, and M. Malavolta, “Micronutrient (Zn, Cu, Fe)-gene interactions in ageing and inflammatory age-related diseases: implications for treatments,” Ageing Research Reviews, vol. 11, no. 2, pp. 297–319, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. A. Madaric, E. Ginter, and J. Kadrabova, “Serum copper, zinc and copper/zinc ratio in males: influence of aging,” Physiological Research, vol. 43, no. 2, pp. 107–111, 1994. View at Google Scholar · View at Scopus
  62. L. J. Lawson, V. H. Perry, P. Dri, and S. Gordon, “Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain,” Neuroscience, vol. 39, no. 1, pp. 151–170, 1990. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Mittelbronn, K. Dietz, H. J. Schluesener, and R. Meyermann, “Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude,” Acta Neuropathologica, vol. 101, no. 3, pp. 249–255, 2001. View at Google Scholar · View at Scopus
  64. M. Olah, S. Amor, N. Brouwer et al., “Identification of a microglia phenotype supportive of remyelination,” Glia, vol. 60, no. 2, pp. 306–321, 2012. View at Publisher · View at Google Scholar · View at Scopus
  65. D. A. DeWitt, G. Perry, M. Cohen, C. Doller, and J. Silver, “Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer's disease,” Experimental Neurology, vol. 149, no. 2, pp. 329–340, 1998. View at Publisher · View at Google Scholar · View at Scopus
  66. L. M. Shaffer, M. D. Dority, R. Gupta-Bansal, R. C. A. Frederickson, S. G. Younkin, and K. R. Brunden, “Amyloid β precursor protein (Aβ) removal by neuroglial cells in culture,” Neurobiology of Aging, vol. 16, no. 5, pp. 737–745, 1995. View at Publisher · View at Google Scholar · View at Scopus
  67. L. Meda, P. Baron, E. Prat et al., “Proinflammatory profile of cytokine production by human monocytes and murine microglia stimulated with β-amyloid[25–35],” Journal of Neuroimmunology, vol. 93, no. 1-2, pp. 45–52, 1999. View at Publisher · View at Google Scholar · View at Scopus
  68. E. J. Remarque, E. L. E. M. Bollen, A. W. E. Weverling-Rijnsburger, J. C. Laterveer, G. J. Blauw, and R. G. J. Westendorp, “Patients with Alzheimer's disease display a pro-inflammatory phenotype,” Experimental Gerontology, vol. 36, no. 1, pp. 171–176, 2001. View at Publisher · View at Google Scholar · View at Scopus
  69. C. A. Colton and D. L. Gilbert, “Production of superoxide anions by a CNS macrophage, the microglia,” FEBS Letters, vol. 223, no. 2, pp. 284–288, 1987. View at Google Scholar · View at Scopus
  70. C. A. Colton, “Heterogeneity of microglial activation in the innate immune response in the brain,” Journal of Neuroimmune Pharmacology, vol. 4, no. 4, pp. 399–418, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Jimenez, D. Baglietto-Vargas, C. Caballero et al., “Inflammatory response in the hippocampus of PS1M146L/APP751SL mouse model of Alzheimer's disease: age-dependent switch in the microglial phenotype from alternative to classic,” Journal of Neuroscience, vol. 28, no. 45, pp. 11650–11661, 2008. View at Publisher · View at Google Scholar · View at Scopus
  72. H. Kimelberg, “Primary astrocyte cultures—a key to astrocyte function,” Cellular and Molecular Neurobiology, vol. 3, no. 1, pp. 1–16, 1983. View at Publisher · View at Google Scholar · View at Scopus
  73. C. Farina, F. Aloisi, and E. Meinl, “Astrocytes are active players in cerebral innate immunity,” Trends in Immunology, vol. 28, no. 3, pp. 138–145, 2007. View at Publisher · View at Google Scholar · View at Scopus
  74. R. E. Mrak, J. G. Sheng, and W. S. T. Griffin, “Correlation of astrocytic S100β expression with dystrophie neurites in amyloid plaques of Alzheimer's disease,” Journal of Neuropathology and Experimental Neurology, vol. 55, no. 3, pp. 273–279, 1996. View at Google Scholar · View at Scopus
  75. C. J. Pike, B. J. Cummings, R. Monzavi, and C. W. Cotman, “β-Amyloid-induced changes in cultured astrocytes parallel reactive astrocytosis associated with senile plaques in Alzeimer's disease,” Neuroscience, vol. 63, no. 2, pp. 517–531, 1994. View at Publisher · View at Google Scholar · View at Scopus
  76. T. Wyss-Coray, J. D. Loike, T. C. Brionne et al., “Adult mouse astrocytes degrade amyloid-β in vitro and in situ,” Nature Medicine, vol. 9, no. 4, pp. 453–457, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. R. Del Bo, N. Angeretti, E. Lucca, M. G. De Simoni, and G. Forloni, “Reciprocal control of inflammatory cytokines, IL-1 and IL-6, β-amyloid production in cultures,” Neuroscience Letters, vol. 188, no. 1, pp. 70–74, 1995. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Johnstone, A. J. H. Gearing, and K. M. Miller, “A central role for astrocytes in the inflammatory response to β- amyloid; chemokines, cytokines and reactive oxygen species are produced,” Journal of Neuroimmunology, vol. 93, no. 1-2, pp. 182–193, 1999. View at Publisher · View at Google Scholar · View at Scopus
  79. G. Forloni, F. Mangiarotti, N. Angeretti, E. Lucca, and M. G. De Simoni, “β-amyloid fragment potentiates IL-6 and TNF-α secretion by LPS in astrocytes but not in microglia,” Cytokine, vol. 9, no. 10, pp. 759–762, 1997. View at Publisher · View at Google Scholar · View at Scopus
  80. J. Hu, K. T. Akama, G. A. Krafft, B. A. Chromy, and L. J. Van Eldik, “Amyloid-β peptide activates cultured astrocytes: morphological alterations, cytokine induction and nitric oxide release,” Brain Research, vol. 785, no. 2, pp. 195–206, 1998. View at Publisher · View at Google Scholar · View at Scopus
  81. C. Haass and D. J. Selkoe, “Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide,” Nature Reviews Molecular Cell Biology, vol. 8, no. 2, pp. 101–112, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. D. M. Walsh and D. J. Selkoe, “Aβ oligomers-a decade of discovery,” Journal of Neurochemistry, vol. 101, no. 5, pp. 1172–1184, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. M. E. Harris, K. Hensley, D. A. Butterfield, R. A. Leedle, and J. M. Carney, “Direct evidence of oxidative injury produced by the Alzheimer's β-amyloid peptide (1–40) in cultured hippocampal neurons,” Experimental Neurology, vol. 131, no. 2, pp. 193–202, 1995. View at Google Scholar · View at Scopus
  84. S. Walter, M. Letiembre, Y. Liu et al., “Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease,” Cellular Physiology and Biochemistry, vol. 20, no. 6, pp. 947–956, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. M. Jana, C. A. Palencia, and K. Pahan, “Fibrillar amyloid-β peptides activate microglia via TLR2: implications for Alzheimer's disease,” Journal of Immunology, vol. 181, no. 10, pp. 7254–7262, 2008. View at Google Scholar · View at Scopus
  86. M. O. Chaney, W. B. Stine, T. A. Kokjohn et al., “RAGE and amyloid beta interactions: atomic force microscopy and molecular modeling,” Biochimica et Biophysica Acta, vol. 1741, no. 1-2, pp. 199–205, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. L. F. Lue, D. G. Walker, L. Brachova et al., “Involvement of microglial receptor for advanced glycation endproducts (RAGE) in Alzheimer's disease: identification of a cellular activation mechanism,” Experimental Neurology, vol. 171, no. 1, pp. 29–45, 2001. View at Publisher · View at Google Scholar · View at Scopus
  88. A. Salminen, J. Ojala, T. Suuronen, K. Kaarniranta, and A. Kauppinen, “Amyloid-β oligomers set fire to inflammasomes and induce Alzheimer's pathology: Alzheimer Review Series,” Journal of Cellular and Molecular Medicine, vol. 12, no. 6, pp. 2255–2262, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. C. S. Jack, N. Arbour, J. Manusow et al., “TLR signaling tailors innate immune responses in human microglia and astrocytes,” Journal of Immunology, vol. 175, no. 7, pp. 4320–4330, 2005. View at Google Scholar · View at Scopus
  90. T. Kielian, “Toll-like receptors in central nervous system glial inflammation and homeostasis,” Journal of Neuroscience Research, vol. 83, no. 5, pp. 711–730, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. M. Song, J. Jin, J. Lim et al., “TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease,” Journal of Neuroinflammation, vol. 8, no. 92, pp. 1–14, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. K. L. Richard, M. Filali, P. Préfontaine, and S. Rivest, “Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid β1-42 and delay the cognitive decline in a mouse model of Alzheimer's disease,” Journal of Neuroscience, vol. 28, no. 22, pp. 5784–5793, 2008. View at Publisher · View at Google Scholar · View at Scopus
  93. K. Tahara, H. Kim, J. Jin, J. A. Maxwell, L. Li, and K. Fukuchi, “Role of toll-like receptor signalling in Aβ uptake and clearance,” Brain, vol. 129, no. 11, pp. 3006–3019, 2006. View at Publisher · View at Google Scholar · View at Scopus
  94. C. R. Stewart, L. M. Stuart, K. Wilkinson et al., “CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer,” Nature Immunology, vol. 11, no. 2, pp. 155–161, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. W. Zhang, L. Wang, J. Yu, Z. Chi, and L. Tan, “Increased expressions of TLR2 and TLR4 on peripheral blood mononuclear cells from patients with Alzheimer's disease,” Journal of the Neurological Sciences, vol. 315, no. 1-2, pp. 67–71, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. A. Bierhaus, D. M. Stern, and P. P. Nawroth, “RAGE in inflammation: a new therapeutic target?” Current Opinion in Investigational Drugs, vol. 7, no. 11, pp. 985–991, 2006. View at Google Scholar · View at Scopus
  97. R. Deane, Z. Wu, and B. V. Zlokovic, “RAGE (Yin) versus LRP (Yang) balance regulates Alzheimer amyloid β-peptide clearance through transport across the blood-brain barrier,” Stroke, vol. 35, no. 11, supplement 1, pp. 2628–2631, 2004. View at Publisher · View at Google Scholar · View at Scopus
  98. J. E. Donahue, S. L. Flaherty, C. E. Johanson et al., “RAGE, LRP-1, and amyloid-beta protein in Alzheimer's disease,” Acta Neuropathologica, vol. 112, no. 4, pp. 405–415, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. O. Arancio, H. P. Zhang, X. Chen et al., “RAGE potentiates Aβ-induced perturbation of neuronal function in transgenic mice,” EMBO Journal, vol. 23, no. 20, pp. 4096–4105, 2004. View at Publisher · View at Google Scholar · View at Scopus
  100. G. Zuliani, M. Ranzini, G. Guerra et al., “Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia,” Journal of Psychiatric Research, vol. 41, no. 8, pp. 686–693, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. J. Ojala, I. Alafuzoff, S. Herukka, T. van Groen, H. Tanila, and T. Pirttilä, “Expression of interleukin-18 is increased in the brains of Alzheimer's disease patients,” Neurobiology of Aging, vol. 30, no. 2, pp. 198–209, 2009. View at Publisher · View at Google Scholar · View at Scopus
  102. J. Apelt and R. Schliebs, “β-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology,” Brain Research, vol. 894, no. 1, pp. 21–30, 2001. View at Publisher · View at Google Scholar · View at Scopus
  103. V. Pétrilli, C. Dostert, D. A. Muruve, and J. Tschopp, “The inflammasome: a danger sensing complex triggering innate immunity,” Current Opinion in Immunology, vol. 19, no. 6, pp. 615–622, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. K. Furukawa, S. W. Barger, E. M. Blalock, and M. P. Mattson, “Activation of K+ channels and suppression of neuronal activity by secreted β-amyloid-precursor protein,” Nature, vol. 379, no. 6560, pp. 74–78, 1996. View at Publisher · View at Google Scholar · View at Scopus
  105. S. P. Yu, Z. S. Farhangrazi, H. S. Ying, C. Yeh, and D. W. Choi, “Enhancement of outward potassium current may participate in β-amyloid peptide-induced cortical neuronal death,” Neurobiology of Disease, vol. 5, no. 2, pp. 81–88, 1998. View at Publisher · View at Google Scholar · View at Scopus
  106. A. Halle, V. Hornung, G. C. Petzold et al., “The NALP3 inflammasome is involved in the innate immune response to amyloid-β,” Nature Immunology, vol. 9, no. 8, pp. 857–865, 2008. View at Publisher · View at Google Scholar · View at Scopus
  107. A. I. Bush, “Metals and neuroscience,” Current Opinion in Chemical Biology, vol. 4, no. 2, pp. 184–191, 2000. View at Publisher · View at Google Scholar
  108. M. C. Linder and M. Hazegh-Azam, “Copper biochemistry and molecular biology,” American Journal of Clinical Nutrition, vol. 63, supplement 5, pp. 797S–811S, 1996. View at Google Scholar · View at Scopus
  109. T. A. Bayer, S. Schäfer, A. Simons et al., “Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Aβ production in APP23 transgenic mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 2, pp. 14187–14192, 2003. View at Publisher · View at Google Scholar · View at Scopus
  110. M. A. Lovell, J. D. Robertson, W. J. Teesdale, J. L. Campbell, and W. R. Markesbery, “Copper, iron and zinc in Alzheimer's disease senile plaques,” Journal of the Neurological Sciences, vol. 158, no. 1, pp. 47–52, 1998. View at Publisher · View at Google Scholar · View at Scopus
  111. M. Schrag, A. Crofton, M. Zabel et al., “Effect of cerebral amyloid angiopathy on brain iron, copper, and zinc in alzheimer's disease,” Journal of Alzheimer's Disease, vol. 24, no. 1, pp. 137–149, 2011. View at Publisher · View at Google Scholar · View at Scopus
  112. D. Noy, I. Solomonov, O. Sinkevich, T. Arad, K. Kjaer, and I. Sagi, “Zinc-amyloid β interactions on a millisecond time-scale stabilize non-fibrillar Alzheimer-related species,” Journal of the American Chemical Society, vol. 130, no. 4, pp. 1376–1383, 2008. View at Publisher · View at Google Scholar · View at Scopus
  113. M. A. Smith, P. L. R. Harris, L. M. Sayre, and G. Perry, “Iron accumulation in Alzheimer disease is a source of redox-generated free radicals,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 18, pp. 9866–9868, 1997. View at Publisher · View at Google Scholar · View at Scopus
  114. C. S. Atwood, R. D. Moir, X. Huang et al., “Dramatic aggregation of alzheimer by Cu(II) is induced by conditions representing physiological acidosis,” Journal of Biological Chemistry, vol. 273, no. 21, pp. 12817–12826, 1998. View at Publisher · View at Google Scholar · View at Scopus
  115. C. S. Atwood, R. C. Scarpa, X. Huang et al., “Characterization of copper interactions with Alzheimer amyloid β peptides: identification of an attomolar-affinity copper binding site on amyloid β1–42,” Journal of Neurochemistry, vol. 75, no. 3, pp. 1219–1233, 2000. View at Publisher · View at Google Scholar · View at Scopus
  116. C. C. Curtain, F. Ali, I. Volitakis et al., “Alzheimer's disease amyloid-β binds copper and zinc to generate an allosterically ordered membrane-penetrating structure containing superoxide dismutase-like subunits,” Journal of Biological Chemistry, vol. 276, no. 23, pp. 20466–20473, 2001. View at Publisher · View at Google Scholar · View at Scopus
  117. X. Huang, C. S. Atwood, R. D. Moir, M. A. Hartshorn, R. E. Tanzi, and A. I. Bush, “Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Aβ peptides,” Journal of Biological Inorganic Chemistry, vol. 9, no. 8, pp. 954–960, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. K. J. Barnham, F. Haeffner, G. D. Ciccotosto et al., “Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease β-amyloid,” FASEB Journal, vol. 18, no. 12, pp. 1427–1429, 2004. View at Publisher · View at Google Scholar · View at Scopus
  119. C. White, J. Lee, T. Kambe, K. Fritsche, and M. J. Petris, “A role for the ATP7A copper-transporting ATPase in macrophage bactericidal activity,” Journal of Biological Chemistry, vol. 284, no. 49, pp. 33949–33956, 2009. View at Publisher · View at Google Scholar · View at Scopus
  120. G. Multhaup, A. Schlicksupp, L. Hesse et al., “The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I),” Science, vol. 271, no. 5254, pp. 1406–1409, 1996. View at Google Scholar · View at Scopus
  121. G. Schmalz, U. Schuster, and H. Schweikl, “Influence of metals on IL-6 release in vitro,” Biomaterials, vol. 19, no. 18, pp. 1689–1694, 1998. View at Publisher · View at Google Scholar · View at Scopus
  122. F. Suska, M. Esposito, C. Gretzer, M. Källtorp, P. Tengvall, and P. Thomsen, “IL-1α, IL-1β and TNF-α secretion during in vivo/ex vivo cellular interactions with titanium and copper,” Biomaterials, vol. 24, no. 3, pp. 461–468, 2003. View at Publisher · View at Google Scholar · View at Scopus
  123. F. Suska, C. Gretzer, M. Esposito et al., “In vivo cytokine secretion and NF-κB activation around titanium and copper implants,” Biomaterials, vol. 26, no. 5, pp. 519–527, 2005. View at Publisher · View at Google Scholar · View at Scopus
  124. T. P. Kennedy, A. J. Ghio, W. Reed et al., “Copper-dependent inflammation and nuclear factor-κb activation by particulate air pollution,” American Journal of Respiratory Cell and Molecular Biology, vol. 19, no. 3, pp. 366–378, 1998. View at Google Scholar · View at Scopus
  125. T. M. Rice, R. W. Clarke, J. J. Godleski et al., “Differential ability of transition metals to induce pulmonary inflammation,” Toxicology and Applied Pharmacology, vol. 177, no. 1, pp. 46–53, 2001. View at Publisher · View at Google Scholar · View at Scopus
  126. D. Bar-Or, G. W. Thomas, R. L. Yukl et al., “Copper stimulates the synthesis and release of interleukin-8 in human endothelial cells: a possible early role in systemic inflammatory responses,” Shock, vol. 20, no. 2, pp. 154–158, 2003. View at Google Scholar · View at Scopus
  127. Y. H. Hung, A. I. Bush, and S. La Fontaine, “Links between copper and cholesterol in Alzheimer's disease,” Frontiers in Physiology, vol. 4, no. 111, pp. 1–18, 2013. View at Google Scholar
  128. D. Terwel, Y. Löschmann, H. H.-J. Schmidt, H. R. Schöler, T. Cantz, and M. T. Heneka, “Neuroinflammatory and behavioural changes in the Atp7B mutant mouse model of Wilson's disease,” Journal of Neurochemistry, vol. 118, no. 1, pp. 105–112, 2011. View at Publisher · View at Google Scholar · View at Scopus
  129. H. P. Liu, W. Y. Lin, W. F. Wang et al., “Genetic variability in copper-transporting P-type adenosine triphosphatase (ATP7B) is associated with Alzheimer's disease in a Chinese population,” Journal of Biological Regulators and Homeostatic Agents, vol. 27, no. 2, pp. 319–327, 2013. View at Google Scholar
  130. R. Squitti and R. Polimanti, “Copper hypothesis in the missing hereditability of sporadic alzheimer's disease: ATP7B gene as potential harbor of rare variants,” Journal of Alzheimer's Disease, vol. 29, no. 3, pp. 493–501, 2012. View at Publisher · View at Google Scholar · View at Scopus
  131. S. B. Solerte, L. Cravello, E. Ferrari, and M. Fioravanti, “Overproduction of IFN-γ and TNF-α from natural killer (NK) cells is associated with abnormal NK reactivity and cognitive derangement in Alzheimer's disease,” Annals of the New York Academy of Sciences, vol. 917, pp. 331–340, 2000. View at Google Scholar · View at Scopus
  132. R. Baron, A. Nemirovsky, I. Harpaz, H. Cohen, T. Owens, and A. Monsonego, “IFN-γ enhances neurogenesis in wild-type mice and in a mouse model of Alzheimer's disease,” FASEB Journal, vol. 22, no. 8, pp. 2843–2852, 2008. View at Publisher · View at Google Scholar · View at Scopus
  133. M. A. Mastrangelo, K. L. Sudol, W. C. Narrow, and W. J. Bowers, “Interferon-γ differentially affects Alzheimer's disease pathologies and induces neurogenesis in triple transgenic-AD mice,” American Journal of Pathology, vol. 175, no. 5, pp. 2076–2088, 2009. View at Publisher · View at Google Scholar · View at Scopus
  134. J. R. Connor, P. Tucker, M. Johnson, and B. Snyder, “Ceruloplasmin levels in the human superior temporal gyrus in aging and Alzheimer's disease,” Neuroscience Letters, vol. 159, no. 1-2, pp. 88–90, 1993. View at Google Scholar · View at Scopus
  135. D. A. Loeffler, P. A. LeWitt, P. L. Juneau et al., “Increased regional brain concentrations of ceruloplasmin in neurodegenerative disorders,” Brain Research, vol. 738, no. 2, pp. 265–274, 1996. View at Publisher · View at Google Scholar · View at Scopus
  136. S. Osaki and D. A. Johnson, “Mobilization of liver iron by ferroxidase (ceruloplasmin),” Journal of Biological Chemistry, vol. 244, no. 20, pp. 5757–5758, 1969. View at Google Scholar · View at Scopus
  137. E. Nemeth, M. S. Tuttle, J. Powelson et al., “Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization,” Science, vol. 306, no. 5704, pp. 2090–2093, 2004. View at Publisher · View at Google Scholar · View at Scopus
  138. A. Venti, T. Giordano, P. Eder et al., “Integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5′-untranslated region,” Annals of the New York Academy of Sciences, vol. 1035, pp. 34–48, 2004. View at Publisher · View at Google Scholar · View at Scopus
  139. O. Myhre, H. Utkilen, N. Duale, G. Brunborg, and T. Hofer, “Metal dyshomeostasis and inflammation in Alzheimer's and Parkinson's diseases: possible impact of environmental exposures,” Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 726954, 19 pages, 2013. View at Publisher · View at Google Scholar
  140. K. M. Acevedo, Y. H. Hung, A. H. Dalziel et al., “Copper promotes the trafficking of the amyloid precursor protein,” Journal of Biological Chemistry, vol. 286, no. 10, pp. 8252–8262, 2011. View at Publisher · View at Google Scholar
  141. G. G. Zucconi, S. Cipriani, R. Scattoni, I. Balgkouranidou, D. P. Hawkins, and K. V. Ragnarsdottir, “Copper deficiency elicits glial and neuronal response typical of neurodegenerative disorders,” Neuropathology and Applied Neurobiology, vol. 33, no. 2, pp. 212–225, 2007. View at Publisher · View at Google Scholar · View at Scopus
  142. W. S. Liang, T. Dunckley, T. G. Beach et al., “Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain,” Physiological Genomics, vol. 28, no. 3, pp. 311–322, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. W. S. Liang, E. M. Reiman, J. Valla et al., “Alzheimer's disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 11, pp. 4441–4446, 2008. View at Publisher · View at Google Scholar
  144. L. Agullo, A. Garcia, and J. Hidalgo, “Metallothionein-I+II induction by zinc and copper in primary cultures of rat microglia,” Neurochemistry International, vol. 33, no. 3, pp. 237–242, 1998. View at Publisher · View at Google Scholar · View at Scopus
  145. P. J. Crouch, L. W. Hung, P. A. Adlard et al., “Increasing Cu bioavailability inhibits Aβ oligomers and tau phosphorylation,” Proceedings of the National Academy of Sciences, vol. 106, no. 2, pp. 381–386, 2009. View at Publisher · View at Google Scholar