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International Journal of Alzheimer's Disease
Volume 2011 (2011), Article ID 537528, 11 pages
Issues Raised Involving the Copper Hypotheses in the Causation of Alzheimer's Disease
1Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
2Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
3Adeona Pharmaceuticals, Ann Arbor, MI 48103, USA
Received 2 April 2011; Revised 4 June 2011; Accepted 10 June 2011
Academic Editor: Rosanna Squitti
Copyright © 2011 George J. Brewer. 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.
- Alzheimer's Association, Alzheimer's Disease Facts and Figures, 2010.
- G. J. Brewer and D. A. Newsome, Toxic Copper: The Newly Discovered Culprit in Alzheimer's Disease and Dementia, Raisin Publishing, LLC, Ann Arbor, Mich, USA, 2010.
- W. Mally and P. Caldwell, Alzheimer's Disease, Key Porter Books, Toronto, Canada, 1998.
- 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.
- A. I. Bush, W. H. Pettingell, G. Multhaup et al., “Rapid induction of Alzheimer Aβ amyloid formation by zinc,” Science, vol. 265, no. 5177, pp. 1464–1467, 1994.
- P. A. Adlard, L. Bica, A. R. White, et al., “Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease,” PLoS ONE, vol. 6, no. 3, article e17669, 2011.
- G. J. Brewer, S. H. Kanzer, E. A. Zimmerman et al., “Subclinical zinc deficiency in Alzheimer's disease and Parkinson's disease,” American Journal of Alzheimer's Disease and other Dementias, vol. 25, no. 7, pp. 572–575, 2010.
- D. Religa, D. Strozyk, R. A. Cherny et al., “Elevated cortical zinc in Alzheimer disease,” Neurology, vol. 67, no. 1, pp. 69–75, 2006.
- G. J. Brewer, F. Askari, R. Dick, et al., “Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine,” Translational Research, vol. 154, no. 2, pp. 70–77, 2009.
- R. Squitti, P. Pasqualetti, G. Dal Forno et al., “Excess of serum copper not related to ceruloplasmin in Alzheimer disease,” Neurology, vol. 64, no. 6, pp. 1040–1046, 2005.
- R. Squitti, G. Barbati, L. Rossi et al., “Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF β-amyloid, and h-tau,” Neurology, vol. 67, no. 1, pp. 76–82, 2006.
- R. Squitti, F. Bressi, P. Pasqualetti et al., “Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease,” Neurology, vol. 72, no. 1, pp. 50–55, 2009.
- D. L. Sparks and B. G. Schreurs, “Trace amounts of copper in water induce β-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 19, pp. 11065–11069, 2003.
- D. L. Sparks, R. Friedland, S. Petanceska et al., “Trace copper levels in the drinking water, but not zinc or aluminum influence CNS Alzheimer-like pathology,” Journal of Nutrition, Health and Aging, vol. 10, no. 4, pp. 247–254, 2006.
- R. Deane, A. Sagare, M. Coma, et al., “A novel role for copper: disruption of LRP-dependent brain Abeta clearence,” in Proceedings of the Annual Meeting of the Society for Neuroscience, San Diego, Calif, USA, 2007.
- M. C. Morris, D. A. Evans, C. C. Tangney et al., “Dietary copper and high saturated and trans fat intakes associated with cognitive decline,” Archives of Neurology, vol. 63, no. 8, pp. 1085–1088, 2006.
- J. F. Quinn, S. Crane, C. Harris, and T. L. Wadsworth, “Copper in Alzheimer's disease: too much or too little?” Expert Review of Neurotherapeutics, vol. 9, no. 5, pp. 631–637, 2009.
- M. Waldman and M. Lamb, Dying for a Hamburger : Modern Meat Processing and the Epidemic of Alzheimer's Disease, Thomas Dune Books/St. Martin's Press, New York, NY, USA, 2005.
- W. Osler, Modern Medicine in Theory and Practice, Lea and Febiger, Philadelphia, Pa, USA, 1910.
- W. R. Gowers, A Manual of Diseases of the Nervous System, P Blakiston, Son, and Co, Philadelphia, Pa, USA, 1888.
- J. Strachey, A. Freud, A. Strachey, and A. Tyson, 24 Volumes Entitled, The Standard Edition of the Complete Psychological Works of Sigmund Freud, Written between 1895 and 1939, The Hogarth Press and the Institute of Psycho-Analysis, London, UK, 1966.
- W. Boyd, A Textbook of Pathology: An Introduction to Medicine, Lea and Febiger, Philadelphia, Pa, USA, 1938.
- C. P. Ferri, M. Prince, C. Brayne et al., “Global prevalence of dementia: a delphi consensus study,” Lancet, vol. 366, no. 9503, pp. 2112–2117, 2005.
- W. B. Grant, “Dietary links to Alzheimer's disease,” Alzheimer's Disease Review, vol. 2, pp. 42–55, 1997.
- X. Huang, C. S. Atwood, M. A. Hartshorn et al., “The Aβ peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction,” Biochemistry, vol. 38, no. 24, pp. 7609–7616, 1999.
- T. J. Nelson and D. L. Alkon, “Oxidation of cholesterol by amyloid precursor protein and β-amyloid peptide,” Journal of Biological Chemistry, vol. 280, no. 8, pp. 7377–7387, 2005.
- 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.
- A. R. White, G. Multhaup, D. Galatis et al., “Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer's disease amyloid precursor protein,” Journal of Neuroscience, vol. 22, no. 2, pp. 365–376, 2002.
- L. M. Sayre, G. Perry, P. L. R. Harris, Y. Liu, K. A. Schubert, and M. A. Smith, “In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals,” Journal of Neurochemistry, vol. 74, no. 1, pp. 270–279, 2000.
- Q. Ma, Y. Li, J. Du et al., “Copper binding properties of a tau peptide associated with Alzheimer's disease studied by CD, NMR, and MALDI-TOF MS,” Peptides, vol. 27, no. 4, pp. 841–849, 2006.
- G. M. Hill, G. J. Brewer, and A. S. Prasad, “Treatment of Wilson's disease with zinc. I. Oral zinc therapy regimens,” Hepatology, vol. 7, no. 3, pp. 522–528, 1987.
- J. M. Holden, W. R. Wolf, and W. Mertz, “Zinc and copper in self-selected diets,” Journal of the American Dietetic Association, vol. 75, no. 1, pp. 23–28, 1979.
- L. M. Klevay, S. J. Reck, and D. F. Barcome, “Evidence of dietary copper and zinc deficiencies,” Journal of the American Medical Association, vol. 241, no. 18, pp. 1916–1918, 1979.
- S. Reiser, J. C. Smith, and W. Mertz, “Indices of copper status in humans consuming a typical American diet containing either fructose or starch,” American Journal of Clinical Nutrition, vol. 42, no. 2, pp. 242–251, 1985.
- G. J. Brewer, R. Danzeisen, B. R. Stern et al., “Letter to the editor and reply: toxicity of copper in drinking water,” Journal of Toxicology and Environmental Health, vol. 13, no. 6, pp. 449–459, 2010.
- R. Danzeisen, B. R. Stern, P. J. Aggett, et al., “Reply to George Brewer letter to the editor: toxicity of copper in drinking water,” Journal of Toxicology and Environmental Health, vol. 13, no. 6, pp. 449–459, 2010.
- National Research Council (U.S.). Committee on Copper in Drinking Water, Copper in Drinking Water, National Academy Press, Washington, D.C., USA, 2000.
- H. Kessler, T. A. Bayer, D. Bach et al., “Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial,” Journal of Neural Transmission, vol. 115, no. 8, pp. 1181–1187, 2008.
- M. Miyata and J. D. Smith, “Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and β-amyloid peptides,” Nature Genetics, vol. 14, no. 1, pp. 55–61, 1996.
- S. Moalem, M. E. Percy, D. F. Andrews et al., “Are hereditary hemochromatosis mutations involved in Alzheimer disease?” American Journal of Medical Genetics, vol. 93, no. 1, pp. 58–66, 2000.
- P. Zambenedetti, G. De Bellis, I. Biunno, M. Musicco, and P. Zatta, “Transferrin C2 variant does confer a risk for Alzheimer's disease in caucasians,” Journal of Alzheimer's Disease, vol. 5, no. 6, pp. 423–427, 2003.
- S. Seshadri, A. Beiser, J. Selhub et al., “Plasma homocysteine as a risk factor for dementia and Alzheimer's disease,” New England Journal of Medicine, vol. 346, no. 7, pp. 476–483, 2002.
- E. Nakano, M. P. Williamson, N. H. Williams, and H. J. Powers, “Copper-mediated LDL oxidation by homocysteine and related compounds depends largely on copper ligation,” Biochimica et Biophysica Acta, vol. 1688, no. 1, pp. 33–42, 2004.
- P. J. Crouch, W. H. Lin, P. A. Adlard et al., “Increasing Cu bioavailability inhibits Aβ oligomers and tau phosphorylation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 2, pp. 381–386, 2009.
- K. Ueda, H. Kawano, Y. Hasuo, and M. Fujishima, “Prevalence and etiology of dementia in a Japanese community,” Stroke, vol. 23, no. 6, pp. 798–803, 1992.
- L. White, H. Petrovitch, G. W. Ross et al., “Prevalence of dementia in older Japanese-American men in Hawaii: the Honolulu-Asia aging study,” Journal of the American Medical Association, vol. 276, no. 12, pp. 955–960, 1996.
- G. M. Hill, G. J. Brewer, and J. E. Juni, “Treatment of Wilson's disease with zinc. II. Validation of oral 64coppper with copper balance,” American Journal of the Medical Sciences, vol. 292, no. 6, pp. 344–349, 1986.
- Y. Nose, B. E. Kim, and D. J. Thiele, “Ctr1 drives intestinal copper absorption and is essential for growth, iron metabolism, and neonatal cardiac function,” Cell Metabolism, vol. 4, no. 3, pp. 235–244, 2006.
- C. Salustri, G. Barbati, R. Ghidoni et al., “Is cognitive function linked to serum free copper levels? A cohort study in a normal population,” Clinical Neurophysiology, vol. 121, no. 4, pp. 502–507, 2010.
- G. J. Brewer, S. H. Kanzer, E. A. Zimmerman, D. F. Celmins, S. M. Heckman, and R. Dick, “Copper and ceruloplasmin abnormalities in Alzheimers disease,” American Journal of Alzheimer's Disease and other Dementias, vol. 25, no. 6, pp. 490–497, 2010.
- N. Arnal, D. O. Cristalli, M. J. T. de Alaniz, and C. A. Marra, “Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives,” Brain Research, vol. 1319, no. C, pp. 118–130, 2010.
- R. Danzeisen, M. Araya, B. Harrison et al., “How reliable and robust are current biomarkers for copper status?” British Journal of Nutrition, vol. 98, no. 4, pp. 676–683, 2007.
- G. J. Brewer, R. D. Dick, V. D. Johnson, et al., “Treatment of Wilson's disease with zinc: XV long-term follow-up studies,” The Journal of Laboratory and Clinical Medicine, vol. 132, no. 4, pp. 264–278, 1998.
- H. Kessler, F. G. Pajonk, P. Meisser et al., “Cerebrospinal fluid diagnostic markers correlate with lower plasma copper and ceruloplasmin in patients with Alzheimer's disease,” Journal of Neural Transmission, vol. 113, no. 11, pp. 1763–1769, 2006.
- 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.
- L. M. Klevay, “Alzheimer's disease as copper deficiency,” Medical Hypotheses, vol. 70, no. 4, pp. 802–807, 2008.
- P. Hedera, J. K. Fink, P. L. Bockenstedt, and G. J. Brewer, “Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin: further support for existence of a new zinc overload syndrome,” Archives of Neurology, vol. 60, no. 9, pp. 1303–1306, 2003.
- P. Hedera, A. Peltier, J. K. Fink, S. Wilcock, Z. London, and G. J. Brewer, “Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin II. The denture cream is a primary source of excessive zinc,” NeuroToxicology, vol. 30, no. 6, pp. 996–999, 2009.