Oxidative damage in Alzheimer’s dementia, and the potential etiopathogenic role of aluminosilicates, microglia and micronutrient interactions

  • Peter H. Evans
  • Eiji Yano
  • Jacek Klinowski
  • Ernst Peterhans
Part of the EXS book series (EXS, volume 62)


While evidence implicating free radical oxidative processes in the etiopathogenesis of Alzheimer’s dementia is accumulating, the specific cellular and biochemical mechanisms involved remain to be identified. The potential pathogenic role of microglial cells in neurodegenerative processes is indicated by the finding that purified murine microglial cells exposed in vitro to various model aluminosilicate particles stimulate the generation of tissue-injurious free radical reactive oxygen metabolites. Analogous inorganic aluminosilicate deposits have been reported to occur in the core of the characteristic senile plaques found in the brains of Alzheimer disease subjects. The possible modulation of free radial oxidative activity by antioxidant micronutrients and pharmacological agents, provides a rational basis for further preventative and therapeutic clinical investigations.


Neurofibrillary Tangle Senile Plaque Paired Helical Filament Murine Microglial Cell Brain Lipid Peroxidation 
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  1. Abalan, F. (1984) Alzheimer’s disease and malnutrition: a new etiological hypothesis. Med. Hypoth. 15: 385–393.CrossRefGoogle Scholar
  2. Afanas’ev, I. B., Korkina, L. G., Briviba, K. K., Gunar, V. I., and Vehchkovskii, B. T. (1989) Protection of cells by rutin and iron-rutin complex against free radical damage, in: Medical, Biochemical and Chemical Aspects of Free Radicals. Hayaishi, O., Niki, E., Kondo, M. and Yoshikawa, T. eds. HHHElsevier, Amsterdam, pp. 515–518.Google Scholar
  3. Ames, B. N., Cathcart, R., Schwiers, E., and Hochstein, P. (1981) Uric acid provides an antioxidant defence in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc. Natl. Acad. Sci. 78: 6858–6862.PubMedCrossRefGoogle Scholar
  4. Anderson, R., and Lukey, P. T. (1987) A biological role for ascorbate in the selective neutralization of extracellular phagocyte-derived oxidants. Ann. NY Acad. Sci. 498: 229–247.PubMedCrossRefGoogle Scholar
  5. Andorn, A. C., Britton, R. S., and Bacon, B. R. (1990) Evidence that lipid peroxidation and total iron are increased in Alzheimer’s brain. Neurobiol. Aging 11: 316.Google Scholar
  6. Anneren, G., Gardner, A., and Lundin, T. (1986) Increased glutathione peroxidase activity in erthyrocytes in patients with Alzheimer’s disease/senile dementia of Alzheimer’s type. Acta Nerol. Scand. 73: 586–589.CrossRefGoogle Scholar
  7. Antila, E., Nordberg, U.-R., Syvaoja, E.-L., and Westermarck, T. (1990) Selenium therapy in Down syndrome (DS): a theory and clinical trial, in: Antioxidants in Therapy and Preventive Medicine. Emerit, I., Packer, L. and Auclair, C. eds. Plenum, NY, pp. 183–186.Google Scholar
  8. Arriagada, P. V., Louis, D. N., Hedly-Whyte, E. T., and Hyman, B. T. (1991) Neurofibrillary tangles and olfactory dysgenesis. Lancet 337: 559.PubMedCrossRefGoogle Scholar
  9. Arthur, J. R., Nicol, F., and Beckett, G. J. (1991) The roles of selenium in thyroid hormone metabolism, in: Trace Elements in Man and Animals (TEMA-7). Momnilovic, B. ed. HHHInst. Med. Res., Zagreb, pp. 7; 3–7Google Scholar
  10. Asayama, K., Dobashi, K., Hayashibe, H., and Kato, K. (1989) Vitamin E protects against thyroxine-induced acceleration of lipid peroxidation in cardiac and skeletal muscles in rats. J. Nutr. Sci. Vitaminol. 35: 407–418.PubMedCrossRefGoogle Scholar
  11. Auerbach, O., Conston, A. S., Garfinkel, L., Parks, V. R., Kaslow, H. D., and Hammond, E. C. (1980) Presence of asbestos bodies in organs other than the lung. Chest 77: 133–137.PubMedCrossRefGoogle Scholar
  12. Banin, E., and Meiri, H. (1990) Toxic effects of alumino-silicates on nerve cells. Neuroscience 39: 171–178.PubMedCrossRefGoogle Scholar
  13. Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., and Freeman, B. A. (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. 87: 1620–1624.PubMedCrossRefGoogle Scholar
  14. Birchall, J. D., and Chappell, J. S. (1988) The chemistry of aluminium and silicon in relation to Alzheimer’s disease. Clin. Chem. 34: 265–267.PubMedGoogle Scholar
  15. Braughler, J. M., Duncan, L. A., and Goodman, T. (1985) Calcium enhances in vitro radical-induced damage to brain synaptosomes, mitochondria, and cultured spinal cord neurons. J. Neurochem. 45: 1288–1293.PubMedCrossRefGoogle Scholar
  16. Burns, A., and Holland, T. (1986) Vitamin E deficiency. Lancet 1: 805–806.PubMedCrossRefGoogle Scholar
  17. Cairns-Smith, A. G. and Hartman, H. eds. (1986) Clay Minerals and the Origin of Life. CUP, Cambridge.Google Scholar
  18. Campbell, A. K. (1983) Intracellular Calcium: Its Universal Role as a Regulator. John Wiley, Chichester.Google Scholar
  19. Campbell, D., Bunker, V. W., Thomas, A. J., and Clayton, B. E. (1989) Selenium and vitamin E status of healthy and institutionalized eldery subjects: analysis of plasma, erythrocytes and platelets. Br. J. Nutr. 62: 221–227.PubMedCrossRefGoogle Scholar
  20. Candy, J. M., Klinowski, J., Perry, R. H., Perry, E. K., Fairbairn, A., Oakley, A. E., Carpenter, T. A., Atack, J. R., Blessed, G., and Edwardson, J. A. (1986a) Aluminosilicates and senile plaque formation in Alzheimer’s disease. Lancet 1: 354–357.PubMedCrossRefGoogle Scholar
  21. Candy, J. M., Oakley, A. E., Watt, F., Grime, G. W., Klinowski, J., Perry, R. H., and Edwardson, J. A. (1986b) A role for aluminium, silicon and iron in the genesis of senile plaques, in: Modern Trends in Aging Research. EURAGE, John Libbey, 147: 443–450.Google Scholar
  22. Cao, G., and Chen, J. (1991) Effects of dietary zinc on free radical generation, lipid peroxidation, and superoxide dismutase in trained mice. Archs Biochem. Biophys. 291: 147–153.CrossRefGoogle Scholar
  23. Carney, J. M., Starke-Reed, P. E., Oliver, C. N., Landum, R. W., Cheng, M. S., Wu, J. F., and Floyd, R. A. (1991) Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-a-phenylnitrone. Proc. Natl. Acad. Sci. 88: 3633–3636.PubMedCrossRefGoogle Scholar
  24. Ceballos, L, Javoy-Agid, F., Delacourte, A., Defossez, A., Nicole, A., and Sinet, P. M. (1990) Parkinson’s disease and Alzheimer’s disease: neurodegenerative disorders due to brain antioxidant system deficiency? in: Antioxidants in Therapy and Preventive Medicine. Emerit, L, Packer, L. and Auclair, C. eds. Plenum, NY, pp. 493–498.CrossRefGoogle Scholar
  25. Clausen, J., Nielson, S. A., and Kristensen, M. (1989) Biochemical and chnical effects of an antioxidative supplementation of geriatric patients. A double Wind study. Biol. Trace. Element Res. 20: 135–151.CrossRefGoogle Scholar
  26. Clayton, B. (1989) Water pollution at Lowermoor North Cornwall. Report of the Lowermoor Incident Health Advisory Group. Cornwall and Isles of Scilly District Health Authority.Google Scholar
  27. Colton, C. A., Colton, J. S., and Gilbert, D. L. (1986) Changes in synaptic transmission produced by hydrogen peroxide. J. Free Rad. Biol. Med. 2: 141–148.CrossRefGoogle Scholar
  28. Davison, A. J., Legault, N. A., and Steele, D. W. (1986) Effect of 6-hydroxydopamine on polymerization of tubulin. Biochem. Pharmacol. 35: 1411–1417.PubMedCrossRefGoogle Scholar
  29. Deloncle, R., Guillard, O., Clanet, F., Courtois, P., and Piriou, A. (1990) Aluminium transfer as glutamate complex through the blood-brain barrier. Biol. Trace Element Res. 25: 39–45.CrossRefGoogle Scholar
  30. Dowson, J. H. (1982) Neuronal lipofuscin accumulation in ageing and Alzheimer dermentia: a pathogenic mechanism? Br. J. Psychiat. 140: 142–148.CrossRefGoogle Scholar
  31. Esiri, M. M., and Wilhams, R. J. P. (1986) Comments on an olfactory source for an environmental influence and possible involvement of aluminium in the development of Alzheimer’s disease. Neurobiol. Aging 7: 582–583.CrossRefGoogle Scholar
  32. Evans, P. H., Campbell, A. K., Yano, E., and Goodman, B. (1987) Phagocytic oxidant stress and antioxidant interactions in the pneumoconioses and dust-induced tumourigenic lung disease, in: Free Radicals, Oxidant Stress and Drug Action. Rice-Evans, C. ed. Richelieu Press, London, pp. 213–235.Google Scholar
  33. Evans, P. H. (1988) Alzheimer’s senile dementia: a radical case of cephaloconiosis. Neurobiol. Aging 9: 225–226.PubMedCrossRefGoogle Scholar
  34. Evans, P. H., Klinowski, J., Yano, E., and Urano, N. (1989a) Alzheimer’s disease: a pathogenic role for aluminosihcate-induced phagocytic free radicals. Free Rad. Res. Comms. 6: 317–321.CrossRefGoogle Scholar
  35. Evans, P. H., Campbell, A. K., Yano, E., and Morgan, L. G. (1989b) Environmental cancer, phagocytic oxidant stress and nutritional interactions, in: Nutritional Impact of Food Processing. Somogyi, J. C. and Muller, H. R. eds: Karger, Basel. Bibl. Nutr. Dieta 43: 313–326.Google Scholar
  36. Evans, P. H., Peterhans, E., Bürge, T., and Klinowski, J. (1990) Aluminosilicate-induced free radical generation by murine brain glial cells in vitro: potential pathogenic and nutritional interactions in Alzheimer’s dementia. Neurobiol. Aging 11: 288.CrossRefGoogle Scholar
  37. Evans, P. H., Klinowski, J., and Yano, E. (1991) Cephaloconiosis: a free radical perspective on the proposed particulate-induced aetiopathogenesis of Alzheimer’s dementia and related disorders. Med. Hypoth. 34: 209–219.CrossRefGoogle Scholar
  38. Evans, P. H., Peterhans, E., Bürge, T., and Klinowski, J. (1992) Aluminosilicate-induced free radical generation by murine brain glial cells in vitro: potential significance in the aetiopathogenesis of Alzheimer’s dementia. Dementia 3: 1–6.Google Scholar
  39. Frautschy, S. A., Baird, A., and Cole, G. M. (1991) Effects of injected Alzheimer -amyloid cores in rat brain. Proc. Natl. Acad. Sci. 88: 8362–8366.PubMedCrossRefGoogle Scholar
  40. Fulton, B., and Jeflfery, E. H. (1990) Absorption and retention of aluminium from drinking water. 1. Effect of citric and ascorbic acid on aluminium tissue levels in rabbits. Fundam. Appl. Toxicol. 14: 788–796.PubMedCrossRefGoogle Scholar
  41. Ganrot, P. O. (1986) Metabohsm and possible health effects of aluminium. Environ. Health Perspect. 65: 363–441.PubMedGoogle Scholar
  42. Garfinkel, D. (1986) Is aging inevitable? The intracellular zinc deficiency hypothesis of aging. Med. Hypoth. 19: 117–137.CrossRefGoogle Scholar
  43. Garry, P. J., Goodwin, J. S., Hunt, W. C., Hooper, E. M., and Leonard, A. G. (1982) Nutritional status in a healthy elderly population: dietary and supplemental intakes. Am. J. Clin. Nutr. 36: 319–331.PubMedGoogle Scholar
  44. Gautrin, D., and Gauthier, S. (1989) Alzheimer’s disease: environmental factors and etiologic hypotheses. Can. J. Neurol. Sci. 16: 375–387.PubMedGoogle Scholar
  45. Gibson, G. E., and Peterson, C. (1987) Calcium and the aging nervous system. Neurobiol. Aging 8: 329–343.PubMedCrossRefGoogle Scholar
  46. Greger, J. L. (1977) Dietary intake and nutritional status in regard to zinc of institutionalized aged. J. Gerontol. 32: 549–553.PubMedGoogle Scholar
  47. Gutteridge, J. M. C., Quinlan, G. J., Clark, L, and Halliwell, B. (1985) Aluminium salts accelerate peroxidation of membrane lipids stimulated by iron salts. Biochim. Biophys. Acta 835: 441–447.PubMedGoogle Scholar
  48. Hall, E. D., Yonkers, P. A., McCall, J. M., and Braughler, J. M. (1988) Effects of the 21-aminosteroid U74006F on experimental head injury in mice. J. Neurosurg. 68: 456–461.PubMedCrossRefGoogle Scholar
  49. Hall, E. D. (1987) Intensive anti-oxidant pretreatment retards motor nerve degeneration. Brain Res. 413: 175–178.PubMedCrossRefGoogle Scholar
  50. Harman, D. (1988) Free radicals in aging. Mol. Cell Biochem. 84: 155–161.PubMedCrossRefGoogle Scholar
  51. Hershey, L. A., Hershey, C. O., and Varnes, A. W. (1984) CSF silicon in dementia: a prospective study. Neurology 34: 1197–1201.PubMedGoogle Scholar
  52. Heyman, A., Wilkinson, W. E., Stafford, J. A., Helms, M. J., Sigmon, A. H., and Weinberg, T. (1984) Alzheimer’s disease: a study of epidemiological aspects. Ann. Neurol. 15: 335–341.PubMedCrossRefGoogle Scholar
  53. Jeandel, C., Nicolas, M. B., Dubios, F., Nabet-Belleville, F., Penin, F., and Cuny, G. (1989) Lipid peroxidation and free radical scavengers in Alzheimer’s disease. Gerontology 35: 275–282.PubMedCrossRefGoogle Scholar
  54. Johnson, G. V. W., Cogdill, K. W., and Jope, R. S. (1990) Oral aluminium alters in vitro protein phosphorylation and kinase activities in rat brain. Neurobiol. Aging. 11: 209–216.PubMedCrossRefGoogle Scholar
  55. Kasa, M., Bierma, T. J., Waterstraat, F., Corsaut, M., and Singh, S. P. (1989) Routine blood chemistry screen: a diagnostic aid for Alzheimer’s disease. Neuroepidemiol. 8: 254–261.CrossRefGoogle Scholar
  56. Kedziora, J., and Bartosz, G. (1988) Down’s syndrome: a pathology involving the lack of balance of reactive oxygen species. Free Rad. Biol. Med. 4: 317–330.PubMedCrossRefGoogle Scholar
  57. Knowles, R. G., Palacios, M., Palmer, R. M. J., and Moncada, S. (1989) Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc. Natl. Acad. Sci. 86: 5159–5162.PubMedCrossRefGoogle Scholar
  58. Kohen, R., Yamamoto, Y., Cundy, K. C., and Ames, B. N. (1988) Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain. Proc. Natl. Acad. Sci. 85: 3175–3179.PubMedCrossRefGoogle Scholar
  59. Korf, J. Gramsbergen, J. B. P., Prenen, G. H. M., and Go, K. G. (1986) Cation shifts and excitotoxins in Alzheimer and Huntington disease and experimental brain damage, in: Progress in Brain Research. Swaab, D. F., Fliers, E., Mirmiran, M., Van Gool, W. A. and Van Haaren, F. eds. Elsevier, Amsterdam, pp. 213–226.Google Scholar
  60. Machlin, L. J. (1989) Use and safety of elevated dosages of vitamin E in adults, in: Elevated Dosages of Vitamins. Benefits and Hazards. Walter, P., Brubacher, G. and Stahehn, H. eds. Hans Huber, Toronto, pp. 56–68.Google Scholar
  61. Martins, R. N., Harper, C. G., Stokes, G. B., and Masters, C. L. (1986) Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer’s disease may reflect oxidative stress. J. Neurochem. 46: 1042–1045.PubMedCrossRefGoogle Scholar
  62. Martyn, C. N., Osmond, C., Edwardson, J. A., Barker, D. J. P., Harris, E. C., and Lacey, R. F. (1989) Geographical relation between Alzheimer’s disease and aluminium in drinking water. Lancet 1: 59–62.PubMedGoogle Scholar
  63. Masters, C. L., Multhaup, G., Simms, G., Pottgiesser, J., Martins, R. N., and Bayreuther, K. (1985) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 4: 2757–2763.PubMedGoogle Scholar
  64. Mattson, M. P., Rychlik, B., and Engle, M. G. (1991) Possible involvement of calcium and inositol phospholipid signaling pathways in neurofibrillary degeneration, in: Alzheimer’s Disease: Basic Mechanisms, Diagnosis and Therapeutic Strategies. Iqbal, K., McLachlan, D. R. C., Winblad, B. and Wisniewski, H. M. eds. Wiley, Chichester, pp. 191–198.Google Scholar
  65. McPherson, A., and Shlichta, P. (1988) Heterogeneous and epitaxial nucleation of protein crystals on mineral surfaces. Science 239: 385–387.PubMedCrossRefGoogle Scholar
  66. McLachlan, D. R. C., Dalton, A. J., Krück, T. P. A., Beh, M. Y., Smith, W. L., Kalow, W., and Andrews, D. F. (1991) Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet 337: 1304–1308.CrossRefGoogle Scholar
  67. Metcalfe, T., Bowen, D. M., and Muller, D. P. R. (1989) Vitamin E concentrations in human brain of patients with Alzheimer’s disease, fetuses with Down’s syndrome, centenarians and controls. Neurochem. Res. 14: 1209–1212.PubMedCrossRefGoogle Scholar
  68. Mortimer, J. A., French, L. R., Hutton, J. T., and Schuman, L. M. (1985) Head injury as a risk factor for Alzheimer’s disease. Neurology 35: 264–267.PubMedGoogle Scholar
  69. Murphy, S. P., Subar, A. F., and Block, G. (1990) Vitamin E intakes and sources in the United States. Am. J. Clin. Nutr. 52: 361–367.PubMedGoogle Scholar
  70. Murreil, J., Farlow, M., Ghetti, B., and Benson, M. D. (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer’s disease. Science 254: 97–99.CrossRefGoogle Scholar
  71. Netter, P., Steinmetz, J., Gillet, P., Kessler, M., Bardin, T., Fener, P., Burnel, D., Gaucher, A., Pourel, J., and Bannwarth, B. (1991) Amorphous aluminosilicates in synovial fluid in dialysis-associated arthropathy. Lancet 337: 554–555.PubMedCrossRefGoogle Scholar
  72. Newsam, J. M. (1986) The zeolite cage structure. Science 231: 1093–1099.PubMedCrossRefGoogle Scholar
  73. Nöda, Y., McGeer, P. L., and McGeer, E. G. (1982) Lipid peroxides in brain during aging and vitamin E deficiency: possible relations to changes in neurotransmitter indices. Neurobiol. Aging 3: 173–178.PubMedCrossRefGoogle Scholar
  74. Ohtawa, M., Seko, M., and Takayama, F. (1983) Effect of aluminum ingestion on lipid peroxidation in rats. Chem. Pharm. Bull. 31: 1415–1418.PubMedCrossRefGoogle Scholar
  75. Osmand, A. P., and Switzer, R. C. (1991) Differential distribution of lactoferrin and Alz-50 immunoreactivites in neuritic plaques and neurofibrillary tangles, in: Alzheimer’s Disease: Basic Mechanisms, Diagnosis and Therapeutic Strategies. Iqbal, K., McLachlan, D. R. C., Winblad, B. and Wisniewski, H. M. eds. Wiley, Chichester, pp. 219–228.Google Scholar
  76. PeUigrini-Giampietro, D. E., Cherici, G., Alesiani, M., Carla, V., and Moroni, F. (1988) Excitatory amino acid release from rat hippocampal slices as a consequence of free-radical formation. J. Neurochem. 51: 1960–1963.CrossRefGoogle Scholar
  77. Pennington, J. A. T. (1987) Aluminium content of foods and diets. Food Additiv. Contam. 5: 161–232.Google Scholar
  78. Perl, D. P., and Good, P. F. (1987) Uptake of aluminium into central nervous system along nasal-olfactory pathways. Lancet 1: 1028.PubMedCrossRefGoogle Scholar
  79. Perry, T. L., Yong, V. W., Bergeron, C., Hansen, S., and Jones, K. (1987) Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer’s disease. Ann. Neurol. 21: 331–336.PubMedCrossRefGoogle Scholar
  80. Perry, V. H., and Gordon, S. (1988) Macrophages and microglia in the nervous system. TINS 11: 273–277.PubMedGoogle Scholar
  81. Pontefract, R. D., and Cunningham, H. M. (1973) Penetration of asbestos through the digestive tract of rats. Nature 243: 352–353.PubMedCrossRefGoogle Scholar
  82. Probst, A., Brunnschweiler, H., Lautenshlager, C., and Ulrich, J. (1987) A special type of senile plaque, possibly an initial stage. Acta Neuropathol. 74: 133–141.PubMedCrossRefGoogle Scholar
  83. Pryor, W. A. (1987) Views on the wisdom of using antioxidant vitamin supplements. Free Rad. Biol. Med. 3: 189–191.PubMedCrossRefGoogle Scholar
  84. Rees, S., and Cragg, B. (1983) Is silica involved in neuritic (senile) plaque formation? Acta Neuropathol. 59: 31–40.PubMedCrossRefGoogle Scholar
  85. Rifat, S. L., Eastwood, M. R., McLachlan D. R. C., and Corey, P. N. (1990) Effect of exposure of miners to aluminium powder. Lancet 336: 1162–1165.PubMedCrossRefGoogle Scholar
  86. Roberts, E. (1986) Alzheimer’s disease may begin in the nose and may be caused by aluminosilicates. Neurobiol. Aging 7: 561–567.PubMedCrossRefGoogle Scholar
  87. Roskams, A. J., and Connor, J. R. (1990) Aluminium access to the brain: a role for transferrin and its receptor. Proc. Natl. Acad. Sci. 87: 9024–9027.PubMedCrossRefGoogle Scholar
  88. Sakamoto, W., Fujie, K., Handa, H., Ogihara, T., and Mino, M. (1990) In vivo inhibition of superoxide production and protein kinase C activity in macrophages from vitamin E-treated rats. Internat. J. Vit. Nutr. Res. 60: 338–342.Google Scholar
  89. Sonderer, B., Wild, P., Wyler, R., Fontana, A., Peterhans, E., and Schwyzer, M. (1987) Murine glia cells in culture can be stimulated to generate reactive oxygen. J. Leukocyte Biol. 42: 463–473.PubMedGoogle Scholar
  90. Stankovic, A., and Mitrovic, D. R. (1991) Aluminum salts stimulate luminol-enhanced chemiluminescence production by human neutrophils. Free Rad. Res. Comms. 14: 47–55.CrossRefGoogle Scholar
  91. Subbarao, K. V., Richardson, J. S., and Ang, L. C. (1990) Autopsy samples of Alzheimer’s cortex show increased peroxidation in vitro. J. Neurochem. 55: 342–345.PubMedCrossRefGoogle Scholar
  92. Tolonen, M., Halme, M., and Sarna, S. (1985) Vitamin E and selenium supplementation in geriatric patients. A double-blind preliminary clinical trial. Biol. Trace Element Res. 7: 161–168.Google Scholar
  93. Trump, B. F., Berezesky, I. K., and Phelps, P. C. (1981) Sodium and calcium regulation and the role of the cystoskeleton in the pathogenesis of disease: a review and hypothesis. Scan. Electron Microscopy 11: 435–454.Google Scholar
  94. Van Rhijn, A. G., Prior, C. A., and Corrigan, F. M. (1990) Dietary supplementation with zinc sulphate, sodium selenite and fatty acids in early dementia of Alzheimer’s type. J. Nutr. Med. 1: 259–266.CrossRefGoogle Scholar
  95. Vogelsang, G. D., Zemlan, F. P., and Dean, G. E. (1989) Hyperpurification of paired helical filaments reveals elevations in hydroxyprohne content and a core structure related peptide fragment, in: Alzheimer’s Disease and Related Disorders. Iqbal, K., Wisniewski, H. M. and Winblad, B., eds. Alan Liss Inc, NY, pp. 791–800.Google Scholar
  96. Volicer, L., and Crino, P. B. (1990) Involvement of free radicals in dementia of the Alzheimer type: a hypothesis. Neurobiol. Aging 11: 567–571.PubMedCrossRefGoogle Scholar
  97. Wallwork, J. C. (1987) Zinc and the central nervous system. Prog. Food Nutr. Soc. 11: 203–247.Google Scholar
  98. Watson, F., Robinson, J., and Edwards, S. W. (1991) Protein kinase C-dependent and -independent activation of the NADPH oxidase of human neutrophils. J. Biol. Chem. 266: 7432–7439.PubMedGoogle Scholar
  99. Wei, E. P., Ellison, M. D., Kontos, H. A., and Povlishock, J. T. (1986) O2 radicals in arachidonate-induced increased blood-brain barrier permeabihty to proteins. Am. J. Physiol. 251: H693–699.Google Scholar
  100. Wenk, G. L., and Stemmer, K. L. (1983) Suboptimal dietary zinc intake increases aluminum accumulation into the rat brain. Brain Res. 288: 393–395.PubMedCrossRefGoogle Scholar
  101. Wenstrup, D., Ehmann, W. D., and Markesbery, W. R. (1990) Trace element imbalances in isolated subcellular fractions of Alzheimer’s disease brains. Brain Res. 533: 125–131.PubMedCrossRefGoogle Scholar
  102. Williams, A. E., and Blakemore, W. F. (1990) Monocyte-mediated entry of pathogens into the central nervous system. Neuropathol. Appl. Neurobiol. 16: 377–392.PubMedCrossRefGoogle Scholar
  103. Willson, R. L. (1989) Zinc and iron in free radical pathology and cellular control, in: Zinc in Human Biology. Mills, C. F. ed. Springer-Verlag, London, pp. 147–172.Google Scholar
  104. 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: 160–162.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 1992

Authors and Affiliations

  • Peter H. Evans
    • 1
  • Eiji Yano
    • 2
  • Jacek Klinowski
    • 3
  • Ernst Peterhans
    • 4
  1. 1.MRC Dunn Nutrition UnitCambridgeEngland
  2. 2.Department of ChemistryUniversity of CambridgeCambridgeEngland
  3. 3.Department of Public HealthTokyo University School of MedicineTokyo 173Japan
  4. 4.Institute of Veterinary VirologyUniversity of BerneBerneSwitzerland

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