131
Views
31
CrossRef citations to date
0
Altmetric
Original Article

Review
Genetics, lifestyle and the roles of amyloid β and oxidative stress in Alzheimer’s disease

, , &
Pages 639-667 | Received 03 Mar 2003, Accepted 21 Aug 2003, Published online: 09 Jul 2009

References

  • ALBERS, D. S., and BEAL, M. F., 2000, Mitochondrial dysfunction and oxidative stress in aging and neurodegenerative disease. Journal of Neural Transmission, Supplement, 59, 133–154.
  • ALZHEIMER, A., 1907, Uber eine eigenartige erkrankung der himrinde. Erkrankung der Himrinde. Allgemeine. Zeitschrift fur Psychiatrie (Berlin), 64, 146–148.
  • ATWOOD, C. S., MOIR, R. D., HUANG, X., SCARPA, R. C., BACARRA, N. M., ROMANO, D. M. et al., 1998, Dramatic aggregation of Alzheimer Abeta by Cu(ii) is induced by conditions representing physio-logical acidosis. Journal of Biological Chemistry, 273, 12817–12826.
  • ATWOOD, C. S., SCARPA, R. C., HUANG, X., MOIR, R. D., JONES, W. D., FAIRLIE, D. P. et al., 2000, Characterization of copper interactions with Alzheimer amyloid beta peptides: identification of an attomolar-affinity copper binding site on amyloid beta 1–42. Journal of Neurochemistry, 75, 1219–1233.
  • ATWOOD, C. S., ROBINSON, S. R., and SMITH, M. A., 2002, Amyloid-beta: redox-metal chelator and antioxidant. Journal of Alzheimer's Disease, 4, 203–214.
  • BACON, B. R., and BRITTON, R. S., 1990, The pathology of hepatic iron overload: a free radical-mediated process? Hepatology, 11, 127–137.
  • BAGCHI, D., GARG, A., KROHN, R. L., BAGCHI, M., TRAN, M. X., and STOHS, S. J., 1997, Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro. Research Communications in Molecular Pathology and Pharmacology, 95, 179–189.
  • BAGCHI, D., GARG, A., KROHN, R. L., BAGCHI, M., BAGCHI, D. J., BALMOORI, J. et al., 1998, Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. General Pharmacology, 30, 771–776.
  • BARBER, A. A., 1966, Lipid peroxidation in rat tissue homogenates: interaction of iron and ascorbic acid as the normal catalytic mechanism. Lipids, 1, 146–151.
  • BARBERGER-GATEAU, P., LETENNEUR, L., DESCHAMPS, V., PERES, K., DARTIGUES, J. F., and RENAUD, S., 2002, Fish, meat, and risk of dementia: cohort study. BMJ, 325, 932–933.
  • BASU, S., 1999, Oxidative injury induced cyclooxygenase activation in experimental hepatotoxicity. Biochemical and Biophysical Research Communications, 254, 764–767.
  • BEAL, M. F., 1996, Mitochondria, free radicals, and neurodegeneration. Current Opinion in Neurobiology, 6, 661–666.
  • BEHL, C., 1997, Amyloid beta-protein toxicity and oxidative stress in Alzheimer's disease. Cell and Tissue Research, 290, 471–480.
  • BEHL C., 2000, Vitamin E protects neurons against oxidative cell death in vitro more effectively than 17-beta estradiol and induces the activity of the transcription factor NF-kappaB. Journal of Neural Transmission, 107, 393–407.
  • BEHL C., 2002, Oestrogen as a neuroprotective hormone. Nature Reviews, Neuroscience, 6, 433–442.
  • BEHL, C., DAVIS, J., COLE, G. M., and SCHUBERT, D., 1992, Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochemical and Biophysical Research Communications, 186, 944–950.
  • BEHL, C., DAVIS, J. B., LESLEY, R., and SCHUBERT, D., 1994, Hydrogen peroxide mediates amyloid beta protein toxicity. Cell, 77, 817–827.
  • BEHL, C., TRAPP, T., SKUTELLA, T., and HOLSBOER, F., 1997, Protection against oxidative stress-induced neuronal cell death — a novel role for ru486. Eur J Neurosci, 9, 912–920.
  • BEHL, C., WIDMANN, M., TRAPP, T., and HOLSBOER, F., 1995, 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochemical and Biophysical Research Communications, 216, 473–482.
  • BENZI, G., and MORETTI, A., 1995, Are reactive oxygen species involved in Alzheimer's disease? Neurobiology of Aging, 16, 661–674.
  • BISAGLIA, M., VENEZIA, V., PICCIOLI, P., STANZIONE, S., PORCILE, C., Russo, C. et al., 2002, Acetaminophen protects hippocampal neurons and PC12 cultures from amyloid beta-peptides induced oxidative stress and reduces NF-kappaB activation. Neurochemistry International, 41, 43–54.
  • BOVERIS, A., and CHANCE, B., 1973, The mitochondrial generation of hydrogen peroxide. General proper-ties and effect of hyperbaric oxygen. Biochemical Journal, 134, 707–716.
  • BRAYNE, C., GILL, C., HUPPERT, F. A., BARKLEY, C., GEHLHAAR, E., GIRLING, D. M., O'CONNOR, D. W. et al., 1998, Vascular risks and incident dementia: results from a cohort study of the very old. Dementia and Geriatric Cognitive Disorders, 9, 175–180.
  • BREWER, G. J., 1997, Effects of acidosis on the distribution of processing of the beta-amyloid precursor protein in cultured hippocampal neurons. Molecular and Chemical Neuropathology, 31, 171–186.
  • BREWER, G. J., 1998, Age-related toxicity to lactate, glutamate, and beta-amyloid in cultured adult neurons. Neurobiology of Aging, 19, 561–568.
  • BUSH, A. I., PETTINGELL, W. H., MULTHAUP, G., D PARADIS, M., VONSATTEL, J. P., GUSELLA, J. F. et al., 1994a, Rapid induction of Alzheimer A-beta amyloid formation by zinc. Science, 265, 1464–1467.
  • BUSH, A. I., PETTINGELL, W. H. JR, DE PARADIS, M., TANZI, R. E., and WASCO, W., 1994b, The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily. Journal of Biological Chemistry, 43,26618–26621.
  • BUTTERFIELD, D. A., 1997, Beta-amyloid-associated free radical oxidative stress and neurotoxicity: impli-cations for Alzheimer's disease. Chemical Research in Toxicology, 10, 495–506.
  • 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, 655–664.
  • BUTTERFIELD, D. A., HENSLEY, K., HARRIS, M., MATTSON, M., and CARNEY, J., 1994, Beta-amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fash-ion: implications to Alzheimer's disease. Biochemical and Biophysical Research Communications, 200, 710–715.
  • BUXBAUM, J. D., SILVERMAN, J. M., SMITH, C. J., KILIFARSKI, M., REICHERT, J., HOLLANDER, E. et al., 2001, Evidence for a susceptibility gene for autism on chromosome 2 and for genetic heterogeneity. American Journal of Human Genetics, 68, 1514–1520.
  • CAI, X. D., GOLDE, T. E., and YOUNKIN, S. G., 1993, Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science, 259, 514–516.
  • CANEVARI, L., CLARK, J. B., and BATES, T. E., 1999, Beta-amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria. FEBS Letters, 457, 131–134.
  • CASLEY, C. S., CANEVARI, L., LAND, J. M., CLARK, J. B., and SHARPE, M. A., 2002, Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. Journal of Neurochemistry, 80, 91–100.
  • CASTELLANI, R. J., SMITH, M. A., NUNOMURA, A., HARRIS, P. L., and PERRY, G., 1999, Is increased redox-active iron in Alzheimer disease a failure of the copper-binding protein ceruloplasmin? Free Radical Biology and Medicine, 26, 1508–1512.
  • CECCHI, C., FIORILLO, C., SORBI, S., LATORRACA, S., NACMIAS, B., BAGNOLI, S. et al., 2002, Oxidative stress and reduced antioxidant defenses in peripheral cells from familial Alzheimer's patients. Free Radical Biology and Medicine, 33, 1372–1379.
  • CHAN, C., DHARMARAJAN, A., ATWOOD, C., HUANG, X., TANZI, R., BUSH, A. et al., 1999, Anti-apoptotic action of Alzheimer beta amyloid. Alzheimer's Reports, 2, 113–119.
  • CHANDRA, V., and PANDAV, R., 1998, Gene—environment interaction in Alzheimer's disease: a potential role for cholesterol. Neuroepidemiology, 17, 225–232.
  • CHARTIER-HARLIN, M. C., CRAWFORD, F., HOULDEN, H., WARREN, A., HUGHES, D., FIDANI, L. et al., 1991, Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature, 353, 844–846.
  • CHEESEMAN, K. H., and SLATER, T. F., 1993, An introduction to free radical biochemistry. British Medical Bulletin, 49, 481–493.
  • CITRON, M., OLTERSDORF, T., HAASS, C., MCCONLOGUE, L., HUNG, A. Y., SEUBERT, P. et al., 1992, Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature, 360, 672–674.
  • CLEMENTS, A., ALLSOP, D., WALSH, D. M., and WILLIAMS, C. H., 1996, Aggregation and metal-binding properties of mutant forms of the amyloid A-beta peptide of Alzheimer's disease. Journal of Neurochemistry, 66, 740–747.
  • CONNOR, J. R., SNYDER, B. S., BEARD, J. L., FINE, R. E., and MUFSON, E. J., 1992, Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. Journal of Neuroscience Research, 31, 327–335.
  • COPANI, A., KoH, J. Y., and COTMAN, C. W., 1991, Beta-amyloid increases neuronal susceptibility to injury by glucose deprivation. NeuroReport, 2, 763–765.
  • CORDER, E. H., SAUNDERS, A. M., STRITTMATTER, W. J., SCHMECHEL, D. E., GASKELL, P. C., SMALL, G. W. et al., 1993, Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science, 261, 921–923.
  • CRAFT, S., ZALLEN, G., and BAKER, L. D., 1992, Glucose and memory in mild senile dementia of the Alzheimer type. Journal of Clinical and Experimental Neuropsychology, 14, 253–267.
  • CRAFT, S., NEWCOMER, J., KANNE, S., DAGOGO-JACK, S., CRYER, P., SHELINE, Y. et al., 1996, Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiology of Aging, 17, 123–130.
  • CRAWFORD, J. G., 1996, Alzheimer's disease risk factors as related to cerebral blood flow. Medical Hypotheses, 46, 367–377.
  • CUAJUNGCO, M. P., GOLDSTEIN, L. E., NUNOMURA, A., SMITH, M. A., Lim, J. T., ATWOOD, C. S. et al., 2000, Evidence that the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of Abeta by zinc. Journal of Biological Chemistry, 275, 19439–19442.
  • CZECH, C., FORSTL, H., HENTSCHEL, F., MONNING, U., BESTHORN, C., GEIGER-KABISCH, C. et al., 1994, Apolipoprotein E-4 gene dose in clinically diagnosed Alzheimer's disease: prevalence, plasma cholesterol levels and cerebrovascular change. European Archives of Psychiatry and Clinical Neuroscience, 243, 291–292.
  • DAVIES, K. J., 1995, Oxidative stress: the paradox of aerobic life. Biochemical Society Symposia, 61, 1–31.
  • DAVIS, J. B., 1996, Oxidative mechanisms in beta-amyloid cytotoxicity. Neurodegeneration, 5, 441–444.
  • DELA MONTE, S. M., and HEDLEY-WHYTE, E. T., 1990, Small cerebral hemispheres in adults with Down's Syndrome: Contributions of developmental arrest and lesions of Alzheimer's disease. Journal of Neuropathology and Experimental Neurology, 49, 509–520.
  • DE LA TORRE, J. C., 1999, Critical threshold cerebral hypoperfusion causes Alzheimer's disease? Acta Neuropathologica (Berlin), 98, 1–8.
  • DEL MAESTRO, R. F., 1980, An approach to free radicals in medicine and biology. Acta Physiologica Scandinavica, Supplementum, 492, 153–168.
  • DIAMOND, B. J., SHIFLETT, S. C., FEIWEL, N., MATHEIS, R. J., NOSKIN, O., RICHARDS, J. A. et al., 2000, Ginkgo biloba extract: mechanisms and clinical indications. Archives of Physical Medicine and Rehabilitation, 81, 668–678.
  • DIANZANI, M. U., and UGAZIO, G., 1978, Lipid peroxidation. In Biochemical Mechanisms of Liver Injury edited by T. F. Slater (London: Academic Press), pp. 669–707.
  • DICKSON, D. W., RUAN, D., CRYSTAL, H., MARK, M. H., DAVIES, P., KRESS, Y. et al., 1991, Hippocampal degeneration differentiates diffuse Lewy Body disease (DLBD) from Alzheimer's disease: light and electron microscopic immunocytochemistry of CA2-3 neurites specific to DLBD. Neurology, 41, 1402–1409.
  • ECKERT, A., HARTMANN, H., and MULLER, W. E., 1993, Beta-amyloid protein enhances the mitogen-induced calcium response in circulating human lymphocytes. FEBS Letters, 330,49–52.
  • EGAN, T. J., ZAK, O., and AISEN, P., 1993, The anion requirement for iron release from transferrin is preserved in the receptor-transferrin complex. Biochemistry, 32, 8162–8167.
  • EHRENWALD, E., CHIsoLm, G. M., and Fox, P. L., 1994, Intact human ceruloplasmin oxidatively modifies low density lipoprotein. Journal of Clinical Investigation, 93, 1493–1501.
  • ESTERBAUER, H., SCHAUR, R. J., and ZOLLNER, H., 1991, Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radical Biology and Medicine, 11, 81–128.
  • EVANS, D. A., FUNKENSTEIN, H. H., ALBERT, M. S., SCHERR, P. A., COOK, N. R., CHOWN, M. J. et al., 1989, Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. Journal of the American Medical Association, 262, 2551–2556.
  • FASSBENDER, K., SIMONS, M., BERGMANN, C., STROICK, M., LUTJOHANN, D., KELLER, P. et al., 2001, Simvastatin strongly reduces levels of Alzheimer's disease beta-amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proceedings of the National Academy of Sciences USA, 98, 5856–5861.
  • FRANCESCHI, C., CHIRICOLO, M., LICASTRO, F., ZANNOTTI, M., MASI, M., MOCCHEGIANI, E. et al., 1988, Oral zinc supplementation in Down's Syndrome: restoration of thymic endocrine activity and of some immune defects. Journal of Mental Deficiency Research, 32, 169–181.
  • FRASER, P. E., NGUYEN, J. T., SUREWICZ, W. K., and KIRSCHNER, D. A., 1991, pH-dependent structural transitions of Alzheimer amyloid peptides. Biophysical Journal, 60, 1190–1201.
  • FUNAHASHI, T., FLOYD, R. A., and CARNEY, J. M., 1994, Age effect on brain pH during ischemia/ reperfusion and pH influence on peroxidation. Neurobiology of Aging, 15, 161–167.
  • GARDNER, H. W., 1989, Soybean lipoxygenase-1 enzymically forms both (9S)- and (135)-hydroperoxides from linoleic acid by a pH-dependent mechanism. Biochimica et Biophysica Acta, 1001, 274–281.
  • GASPARINI, L., BENUSSI, L., BIANCHETTI, A., BINETTI, G., CURTI, D., GOVONI, S. et al., 1999, Energy metabolism inhibition impairs amyloid precursor protein secretion from Alzheimer's fibroblasts. Neuroscience Letters, 263, 197–200.
  • GEARING, M., MORI, H. MIRRA, S. S., 1996, Abeta-peptide length and apolipoprotein E genotype in Alzheimer's disease. Annals of Neurology, 39, 395–399.
  • GEDDES, J. F., 1997, What's new in the diagnosis of head injury? Journal of Clinical Pathology, 50, 271–274.
  • GENAZZANI, A. R., and GAMBACCIANI M., 1999, Hormone replacement therapy: the perspectives for the 21st century. Maturitas, 32, 11–17.
  • GENOVESI, G., PAOLINI, P., MARCELLINI, L., VERNILLO, E., SALVATI, G., POLIDORI, G. et al., 1996, Relationship between autoimmune thyroid disease and Alzheimer's disease. Panminerva Medica, 38, 61–63.
  • GENTLEMAN, S., and ROBERTS, G., 1992, Risk factors in Alzheimer's disease. BMJ, 304, 118–119.
  • GIBSON, G., MARTINS, R., BLASS, J., and GANDY, S., 1996, Altered oxidation and signal transduction systems in fibroblasts from Alzheimer patients. Life Sciences, 59, 477–489.
  • GIBSON, G. E., SHEU, K. F., and BLASS, J. P., 1998, Abnormalities of mitochondrial enzymes in Alzheimer disease. Journal of Neural Transmission, 105, 855–870.
  • GLENNER, G. G., and WONG, C. W., 1984, Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochemical and Biophysical Research Communications, 120, 885–890.
  • GOATE, A., CHARTIER-HARLIN, M. C., MULLAN, M., BROWN, J., CRAWFORD, F., FIDANI, L. et al., 1991, Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349, 704–706.
  • GOLDSTEIN, I. M., KAPLAN, H. B., EDELSON, H. S., and WEISSMANN, G., 1979a, Ceruloplasmin. A scavenger of superoxide anion radicals. Journal of Biological Chemistry, 254, 4040–4045.
  • GOLDSTEIN, I. M., KAPLAN, H. B., EDELSON, H. S., and WEISSMANN, G., 1979b, A new function for ceruloplasmin as an acute-phase reactant in inflammation: a scavenger of superoxide anion radicals. Transactions of the Association of American Physicians, 92, 360–369.
  • GRANT, W. B., 1999, Dietary links to Alzheimer's disease: 1999 update. Journal of Alzheimer's Disease, 1, 197–201.
  • GRAVES, A. B., LARSON, E. B., EDLAND, S. D., BOWEN, J. D., MCCORMICK, W. C., MCCURRY, S. M. et al., 1996, Prevalence of dementia and its subtypes in the Japanese American population of King County, Washington state. The Kame Project. American Journal of Epidemiology, 144, 760–771.
  • GRIFFITHS, E. J., and HALESTRAP, A. P., 1993, Protection by cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. Journal of Molecular and Cellular Cardiology, 25, 1461–1469.
  • GUO, Z., VIITANEN, M., FRATIGLIONI, L., and WINBLAD, B., 1996, Low blood pressure and dementia in elderly people: the Kungsholmen project. BMJ, 312, 805–808.
  • GUTTERIDGE, J. M., and HALLIWELL, B., 1990, The measurement and mechanism of lipid peroxidation in biological systems. Trends in Biochemical Sciences, 15, 129–135.
  • HAASS, C., HUNG, A. Y., SELKOE, D. J., and TEPLOW, D. B., 1994, Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid beta-protein precursor. Journal of Biological Chemistry, 269, 17741–17748.
  • HALEY, R. W., and DIETSCHY, J. M., 2000, Is there a connection between the concentration of cholesterol circulating in plasma and the rate of neuritic plaque formation in Alzheimer disease? Archives of Neurology, 57, 1410–1412.
  • HALLIWELL, B., 1985, Use of desferrioxamine as a 'probe' for iron-dependent formation of hydroxyl radicals. Evidence for a direct reaction between desferal and the superoxide radical. Biochemical Pharmacology, 34, 229–233.
  • HALLIWELL, B., 1997, Antioxidants and human disease: a general introduction. Nutrition Reviews, 55, S44—S49; disc: S49—S52.
  • HALLIWELL, B., 1999, Establishing the significance and optimal intake of dietary antioxidants: the bio-marker concept. Nutrition Reviews, 57, 104–113.
  • HALLIWELL, B., and GUTTERIDGE, J. M., 1984, Oxygen toxicity, oxygen radicals, transition metals and disease. Biochemical Journal, 219, 1–14.
  • HALLIWELL, B. and GUTTERIDGE, J. M. C. Free Radicals in Biology and Medicine (2nd ed.), Clarenden Press, 1989.
  • HALLIWELL, B., and GUTTERIDGE, J. M., 1990, Role of free radicals and catalytic metal ions in human disease: an overview. Methods in Enzymology, 186, 1–85.
  • HALLIWELL, B., and GUTTERIDGE, J. M., 1992, Biologically relevant metal ion-dependent hydroxyl radical generation. An update. FEBS Letters, 307, 108–112.
  • HALLIWELL, B., GUTTERIDGE, J. M., and CROSS, C. E., 1992, Free radicals, antioxidants, and human disease: where are we now? Journal of Laboratory and Clinical Medicine, 119, 598–620.
  • HANLON, M. C., and SEYBERT, D. W., 1997, The pH dependence of lipid peroxidation using water-soluble azo initiators. Free Radical Biology and Medicine, 23, 712–719.
  • HARDY, J., 1997, The alzheimer family of diseases: many etiologies, one pathogenesis? Proceedings of the National Academy of Sciences USA, 94, 2095–2097.
  • HARDY, J., and ALLSOP, D., 1991, Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends in Pharmacological Sciences, 12, 383–388.
  • HARDY, J. A., WESTER, P., WINBLAD, B., GEZELIUS, C., BRING, G., and ERIKSSON, A., 1985, The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissue. Journal of Neural Transmission, 61, 253–264.
  • HARMAN, D., 1956, Aging: a theory based on free radical and radiation chemistry. Journal of Gerontology, 11, 298–300.
  • HARMAN, D., 1988, Free radicals in aging. Molecular and Cellular Biochemistry, 84, 155–161.
  • HEDLEY, R., HALLMAYER, J., GROTH, D. M., BROOKS, W. S., GANDY, S. E., and MARTINS, R. N., 2002, Association of interleukin-1 polymorphisms with Alzheimer's disease in Australia. Annals of Neurology, 51, 795–797.
  • HEININGER, K., 2000, A unifying hypothesis of Alzheimer's disease. IV. Causation and sequence of events. Reviews in the Neurosciences, 11, 213–328.
  • HENDRIE, H. C., HALL, K. S., Hui, S., UNYERZAGT, F. W., Yu, C. E., LAHIRI, D. K. et al., 1995a, Apolipoprotein E genotypes and Alzheimer's disease in a community study of elderly African Americans. Annals of Neurology, 37, 118–120.
  • HENDRIE, H. C., OSTJNTOKUN, B. O., HALL, K. S., OGUNNIYI, A. O., Hui, S. L., UNYERZAGT, F. W. et al., 1995b, Prevalence of Alzheimer's disease and dementia in two communities: Nigerian Africans and African Americans. American Journal of Psychiatry, 152, 1485–1492.
  • HENSLEY, K., BUTTERFIELD, D. A., HALL, N., COLE, P., SUBRAMANIAM, R., MARK, R. et al., 1996, Reactive oxygen species as causal agents in the neurotoxicity of the Alzheimer's disease-associated amyloid beta peptide. Annals of the New York Academy of Sciences, 786, 120–134.
  • 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. Annals of Neurology, 15, 335–341.
  • HEYMAN, A., FILLENBAUM, G. G., WELSH-BOHMER, K. A., GEARING, M., MIRRA, S. S., MOHS, R. C. et al., 1998, Cerebral infarcts in patients with autopsy-proven Alzheimer's disease: CERAD, part XVIII. Consortium to Establish a Registry for Alzheimer's Disease. Neurology, 51, 159–162.
  • HILBICH, C., KISTERS-WOIKE, B., REED, J., MASTERS, C. L., and BEYREUTHER, K. 1991, Aggregation and secondary structure of synthetic amyloid beta A4 peptides of Alzheimer's disease. Journal of Molecular Biology, 218, 149–163.
  • HILBICH, C., KISTERS-WOIKE, B., REED, J., MASTERS, C. L., and BEYREUTHER, K., 1992, Substitutions of hydrophobic amino acids reduce the amyloidogenicity of Alzheimer's disease beta A4 peptides. Journal of Molecular Biology, 228, 460–473.
  • HIRAI, K., ALIEV, G., NUNOMURA, A., FUJIOKA, H., RUSSELL, R. L., ATWOOD, C. S. et al., 2001, Mitochondrial abnormalities in Alzheimer's disease. Journal of Neuroscience, 21, 3017–3023.
  • HORWOOD, N., and DAVIES, D. C., 1994, Immunolabelling of hippocampal microvessel glucose trans- porter protein is reduced in Alzheimer's disease. Virchows Archiv, 425, 69–72.
  • HOWLAND, D. S., TRUSKO, S. P., SAVAGE, M. J., REAUME, A. G., LANG, D. M., HIRSCH, J. D. et al., 1998, Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol. Journal of Biological Chemistry, 273, 16576–16582.
  • HOWLETT, D. R., JENNINGS, K. H., LEE, D. C., CLARK, M. S., BROWN, F., WETZEL, R. et al., 1995, Aggregation state and neurotoxic properties of Alzheimer beta-amyloid peptide. Neurodegeneration, 4, 23–32.
  • HOYER, S., OESTERREICH, K., and WAGNER, O., 1988, Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? Journal of Neurology, 235, 143–148.
  • HUANG, X., ATWOOD, C. S., MOIR, R. D., HARTSHORN, M. A., VONSATTEL, J. P., TANZI, R. E. et al., 1997, Zinc-induced Alzheimer's Abetal-40 aggregation is mediated by conformational factors. Journal of Biological Chemistry, 272, 26464–26470.
  • HUANG, X., ATWOOD, C. S., HARTSHORN, M. A., MULTHAUP, G., GOLDSTEIN, L. E., SCARPA, R. C. et al., 1999a, The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry, 38, 7609–7616.
  • HUANG, X., CUAJUNGCO, M. P., ATWOOD, C. S., HARTSHORN, M. A., TYNDALL, J. D., HANSON, G. R. et al., 1999b, Cu(ii) potentiation of Alzheimer Abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. Journal of Biological Chemistry, 274, 37111–37116.
  • IBARRETA, D., URCELAY, E., PARRILLA, R., and AYUSO, M. S., 1998, Distinct pH homeostatic features in lymphoblasts from Alzheimer's disease patients. Annals of Neurology, 44, 216–222.
  • IMLAY, J. A., CHIN, S. M., and LINN, S., 1988, Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science, 240, 640–642.
  • INESTROSA, N. C., MARZOLO, M. P., and BONNEFONT, A. B., 1998, Cellular and molecular basis of estrogen's neuroprotection. Potential relevance for Alzheimer's disease. Molecular Neurobiology, 17, 73–86.
  • JAFFE, A. B., TORAN-ALLERAND, C. D., GREENGARD, P., and GANDY, S. E., 1994, Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. Journal of Biological Chemistry, 269, 13065–13068.
  • JARVIK, G. P., WIJSMAN, E. M., KUKULL, W. A., SCHELLENBERG, G. D., Yu, C., and LARSON, E. B., 1995, Interactions of apolipoprotein E genotype, total cholesterol level, age, and sex in prediction of Alzheimer's disease: a case-control study. Neurology, 45, 1092–1096.
  • JORM, A. F., VAN DUIJN, C. M., CHANDRA, V., FRATIGLIONI, L., GRAVES, A. B., HEYMAN et al., 1991, Psychiatric history and related exposures as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. Eurodem risk factors research group. International Journal of Epidemiology, 20, S43—S47.
  • JUAN, S. H., and AUST, S. D., 1999, Mutational analysis of loading of iron into rat liver ferritin by ceruloplasmin. Archives of Biochemistry and Biophysics, 361, 295–301.
  • KALARIA, R. N., HARSHBARGER-KELLY, M., COHEN, D. L., and PREMKUMAR, D. R., 1996, Molecular aspects of inflammatory and immune responses in Alzheimer's disease. Neurobiology of Aging, 17, 687–693.
  • KALMIJN, S., LAUNER, L. J., OTT, A., WITTEMAN, J. C., HOFMAN, A., and BRETELER, M. M., 1997, Dietary fat intake and the risk of incident dementia in the Rotterdam study. Annals of Neurology, 42, 776–782.
  • KANG, J., LEMAIRE, H. G., UNTERBECK, A., SALBAUM, J. M., MASTERS, C. L., GRZESCHIK, K. H. et al., 1987, The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 325, 733–736.
  • KANOWSKI, S., HERRMANN, W. M., STEPHAN, K., WIERICH, W., and HOR RR., 1996, Proof of efficacy of the ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry, 29, 47–56.
  • KATZMAN, R., 1986, Alzheimer's disease. New England Journal of Medicine, 314, 964–973.
  • KATZMAN, R., TERRY, R., DETERESA, R., BROWN, T., DAVIES, P., FULD, P. et al., 1988, Clinical, patho-logical, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Annals of Neurology, 23, 138–144.
  • KEHRER, J. P., 1993, Free radicals as mediators of tissue injury and disease. Critical Reviews in Toxicology, 23, 21–48.
  • KITAGUCHI, N., TAKAHASHI, Y., TOKUSHIMA, Y., SHIOJIRI, S., and ITo, H., 1988, Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature, 331, 530–532.
  • KLAIBER, E. L., BROVERMAN, D. M., VOGEL, W., KOBAYASHI, Y., 1979, Estrogen therapy for severe persistent depressions in women. Archives of General Psychiatry, 36, 550–554.
  • KOH, J. Y., 2001, Zinc and disease of the brain. Molecular Neurobiology, 24, 99–106.
  • KOX, J. Y., YANG, L. L., and COTMAN, C. W., 1990, Beta-amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage. Brain Research, 533, 315–320.
  • KOKMEN, E., BEARD, C. M., CHANDRA, V., OFFORD, K. P., SCHOENBERG, B. S., and BALLARD, D. J., 1991, Clinical risk factors for Alzheimer's disease: a population-based case-control study. Neurology, 41, 1393–1397.
  • KOLSCH, H., LUDWIG, M., LUTJOHANN, D., and RAO, M. L., 2001, Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradio1-17beta. Journal of Neural Transmission, 108, 475–488.
  • KOO, E. H., and SQUAZZO, S. L., 1994, Evidence that production and release of amyloid beta-protein involves the endocytic pathway. Journal of Biological Chemistry, 269, 17386–17389.
  • KOWALTOWSKI, A. J., and VERCESI, A. E., 1999, Mitochondrial damage induced by conditions of oxida-tive stress. Free Radical Biology and Medicine, 26, 463–471.
  • LAWS, S. M., HONE, E., TADDEI, K., HARPER, C., DEAN, B., MCCLEAN, C., MASTERS, C., LAUTENSCHLAGER, N., GANDY, S. E. and MARTINS, R. N., 2002, Variation at the apoe —491 promoter locus is associated with altered brain levels of apolipoprotein e. Mol Psychiatry, 7, 886–890.
  • LAWS, S. M., TADDEI, K., MARTINS, G., PATON, A., FISHER, C., CLARNETTE, R. et al., 1999, The —491AA polymorphism in the ApoE gene is associated with increased plasma ApoE levels in Alzheimer's disease. NeuroReport, 10, 879–882.
  • LE BARS, P. L., KIESER, M., and ITiL, K. Z., 2000, A 26-week analysis of a double-blind, placebo-controlled trial of the ginkgo biloba extract Egb 761 in dementia. Dementia and Geriatric Cognitive Disorders, 11, 230–237.
  • LEHTONEN, A., and LUUTONEN, S., 1986, High-density lipoprotein cholesterol levels of very old people in the diagnosis of dementia. Age and Ageing, 15, 267–270.
  • LEVY-LAHAD, E., LAHAD, A., WIJSMAN, E. M., BIRD, T. D., and SCHELLENBERG, G. D., 1995, Apolipoprotein E genotypes and age of onset in early-onset familial Alzheimer's disease. Annals of Neurology, 38, 678–680.
  • LIM, G. P., CHU, T., YANG, F., BEECH, W., FRAUTSCHY, S. A., and COLE, G. M., 2001, The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. Journal of Neuroscience, 21, 8370–8377.
  • LOCKHART, B. P., BENICOURT, C., JUNIEN, J. L., and PRIVAT, A., 1994, Inhibitors of free radical forma-tion fail to attenuate direct beta-amyloid 25-35 peptide-mediated neurotoxicity in rat hippocampal cultures. Journal of Neuroscience Research, 39, 494–505.
  • LOPEZ, M. F., and MELOV, S., 2002, Applied proteomics: mitochondrial proteins and effect on function. Circulation Research, 90, 380–389.
  • LORENZO, A., and YANKNER, B. A., 1994, Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proceedings of the National Academy of Sciences USA, 91, 12243–12247.
  • LUGASI, A., HORVAHOVICH, P., and DWORSCHAK, E., 1999, Additional information to the in vitro anti- oxidant activity of ginkgo biloba 1. Phytotherapy Research, 13, 160–162.
  • MABROUK, A. F., and DUGAN, L. R., 1960, A kinetic study of the autoxidation of methyl linoleate and linoleic acid emulsions in the presence of sodium chloride. Journal of the American Oil Chemists' Society, 37, 486–490.
  • MANTYH, P. W., GHILARDI, J. R., ROGERS, S., DEMASTER, E., ALLEN, C. J., STIMSON, E. R. et al., 1993, Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. Journal of Neurochemistry, 61, 1171–1174.
  • MARK, R. J., PANG, Z., GEDDES, J. W., UCHIDA, K., and MATTSON, M. P., 1997, Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. Journal of Neuroscience, 17, 1046–1054.
  • MARKESBERY, W. R., 1997, Oxidative stress hypothesis in Alzheimer's disease. Free Radical Biology and Medicine, 23, 134–147.
  • MARKESBERY, W. R., and EHMANN, W. D., 1994, Brain trace elements in Alzheimer's disease. In Alzheimer's Disease, edited by R. D. Terry, R. Katzman and K. L. Bick (New York: Raven), pp. 353–367.
  • 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. Journal of Neurochemistry, 46, 1042–1045.
  • MARTINS, R. N., CLARNETTE, R., FISHER, C., BROE, G. A., BROOKS, W. S., MONTGOMERY, P. et al., 1995, ApoE genotypes in Australia: roles in early and late onset Alzheimer's disease and Down's syndrome. NeuroReport, 6, 1513–1516.
  • MASSAFRA, C., GIOIA, D., DE FELICE, C., PICCIOLINI, E., DE LEO, V., BONIFAZI, M. etal., 2000, Effects of estrogens and androgens on erythrocyte antioxidant superoxide dismutase, catalase and gluta- thione peroxidase activities during the menstrual cycle. Journal of Endocrinology, 167, 447–452.
  • MASTERS, C. L., Simms, G., w — EINMAN, N. A., MULTHAUP, G., MCDONALD, B. L., and BEYREUTHER, K., 1985, Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proceedings of the National Academy of Sciences USA, 82, 4245–4249.
  • MATTSON, M. P., 1990, Antigenic changes similar to those seen in neurofibrillary tangles are elicited by glutamate and Ca2± influx in cultured hippocampal neurons. Neuron, 4, 105–117.
  • MATTSON, M. P., 1995, Untangling the pathophysiochemistry of beta-amyloid. Nature Structural Biology, 2, 926–928.
  • MATTSON, M. P., 1997, Central role of oxyradicals in the mechanism of amyloid beta-peptide cytotoxicity. Alzheimer Disease Review, 2, 1–14.
  • MATTSON, M. P., 2000, Existing data suggest that Alzheimer's disease is preventable. Annals of the New York Academy of Sciences, 924, 153–159.
  • MATTSON, M. P., BARGER, S. W., CHENG, B., LIEBURG, I., SMITH-SWINTOSKY, L., V. and RYDEL, R. E., 1993, Beta amyloid precursor protein metabolites and loss of neuronal ca2+ homeostasis in alzheimer's disease. Tins, 16, 409–414.
  • MATTSON, M. P., CHENG, B., DAVIS, D., BRYANT, K., LIEBERBURG, I., and RYDEL, R. E., 1992, Beta-amyloid peptides destabilise calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. Journal of Neuroscience, 12, 376–389.
  • MATTSON, M. P., LOVELL, M. A., FURUKAWA, K., and MARKESBERY, W. R., 1995, Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2± concentra-tion, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons. Journal of Neurochemistry, 65, 1740–1751.
  • MATTSON, M. P., Guo, Q., FURUKAWA, K., and PEDERSEN, W. A., 1998, Presenilins, the endoplasmic reticulum, and neuronal apoptosis in Alzheimer's disease. Journal of Neurochemistry, 70, 1–14.
  • MATTSON, M. P., DUAN, W., LEE, J., and Guo, Z., 2001a, Suppression of brain aging and neurodegen-erative disorders by dietary restriction and environmental enrichment: molecular mechanisms. Mechanisms of Ageing and Development, 122, 757–778.
  • MATTSON, M. P., DUAN, W., PEDERSEN, W. A., and CULMSEE, C., 2001b, Neurodegenerative disorders and ischemic brain diseases. Apoptosis, 6, 69–81.
  • MAURER, K., lin., R., DIERKS, T., and FROLICH, L., 1997, Clinical efficacy of ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type. Journal of Psychiatric Research, 31, 645–655.
  • MCCAY, P. B., 1985, Vitamin E: interactions with free radicals and ascorbate. Annual Review of Nutrition, 5, 323–340.
  • MCEWEN, B. S., ALVES, S. E., BULLOCH, K., and WEILAND, N. G., 1997, Ovarian steroids and the brain: implications for cognition and aging. Neurology, 48 (Suppl. 7), S8—S15.
  • MCGEER, P. L., and MCGEER, E. G., 2001, Polymorphisms in inflammatory genes and the risk of Alzheimer disease. Archives of Neurology, 58, 1790–1792.
  • MILLER, D. L., PAPAYANNOPOULOS, I. A., STYLES, J., BOBIN, S. A., LIN, Y. Y., BIEMANN, K. et al., 1993, Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. Archives of Biochemistry and Biophysics, 301, 41–52.
  • MIRANDA, S., OPAZO, C., LARRONDO, L. F., MUNOZ, F. J., Ruiz, F., LEIGHTON, F. et al., 2000, The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer's disease. Progress in Neurobiology, 62, 633–648.
  • MISONOU, H., MORISHIMA-KAWASHIMA, M., and IHARA, Y., 2000, Oxidative stress induces intracellular accumulation of amyloid beta-protein (Abeta) in human neuroblastoma cells. Biochemistry, 39, 6951–6959.
  • MIYATA, M., and SMITH, J. D., 1996, Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nature Genetics, 14, 55–61.
  • MONTINE, T. J., MARICESBERY, W. R., MORROW, J. D., and ROBERTS, L. J., II, 1998, Cerebrospinal fluid F2-isoprostane levels are increased in Alzheimer's disease. Annals of Neurology, 44, 410–413.
  • MORRIS, M. C., EVANS, D. A., BIENIAS, J. L., TANGNEY, C. C., BENNETT, D. A., AGGARWAL, N. et al., 2002, Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. Journal of the American Medical Association, 287, 3230–3237.
  • MULTHAUP, G., RUPPERT, T., SCHLICKSUPP, A., HESSE, L., BILL, E., PIPKORN, R. et al., 1998, Copper-binding amyloid precursor protein undergoes a site-specific fragmentation in the reduction of hydrogen peroxide. Biochemistry, 37, 7224–7230.
  • MUNCH, G., Simm, A., DOUBLE, K. L., and RIEDERER, P., 1996, Oxidative stress and advanced glycation endproducts—parts of a vicious circle of neurodegeneration. Alzheimer's Disease Reviews, 1, 71–74.
  • MURRELL, 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.
  • MUSCI, G., BONACCORSI DI PATTI, M. C., and CALABRESE, L., 1993a, The state of the copper sites in human ceruloplasmin. Archives of Biochemistry and Biophysics, 306, 111–118.
  • MUSCI, G., BONACCORSI DI PATTI, M. C., FAGIOLO, U., and CALABRESE, L., 1993b, Age-related changes in human ceruloplasmin. Evidence for oxidative modifications. Journal of Biological Chemistry, 268, 13388–13395.
  • NAGY, Z., ESIRI, M. M., JOBST, K. A., MORRIS, J. H., KING, E. M., MCDONALD, B. et al., 1997, The effects of additional pathology on the cognitive deficit in Alzheimer disease. Journal of Neuropathology and Experimental Neurology, 56, 165–170.
  • NUNOMURA, A., PERRY, G., HIRAI, K., ALIEV, G., TAICEDA, A., CHIBA, S. et al., 1999, Neuronal RNA oxidation in Alzheimer's disease and Down's syndrome. Annals of the New York Academy of Sciences, 893, 362–364.
  • NUNOMURA, A., PERRY, G., PAPPOLLA, M. A., FRIEDLAND, R. P., HIRAI, K., CHIBA, S. et al., 2000, Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. Journal of Neuropathology and Experimental Neurology, 59, 1011–1017.
  • NUNOMURA, A., PERRY, G., ALIEV, G., HIRAI, K., TAKEDA, A., BALRAJ, E. K. et al., 2001, Oxidative damage is the earliest event in Alzheimer disease. Journal of Neuropathology and Experimental Neurology, 60, 759–767.
  • OHKURA, T., IssE, K., AKAZAWA, K., HAMAMOTO, M., YAOI, Y., HAGINO, N., 1995, Long-term estrogen replacement therapy in female patients with dementia of the Alzheimer type: 7 case reports. Dementia, 6, 99–107.
  • OKEN, B. S., STORZBACH, D. M., and KAYE, J. A., 1998, The efficacy of ginkgo biloba 011 cognitive function in Alzheimer disease. Archives of Neurology, 55, 1409–1415.
  • OLIVIERI, G., NOVAKOVIC, M., SAVASKAN, E., MEIER, F., BAYSANG, G., BROCKHAUS, M. et al., 2002, The effects of beta-estradiol on SHSY5Y neuroblastoma cells during heavy metal induced oxidative stress, neurotoxicity and beta-amyloid secretion. Neuroscience, 113, 849–855.
  • OTT, A., BRETELER, M. M., VAN HARSKAMP, F., CLAUS, J. J., VAN DER CAMMEN, T. J., GROBBEE, D. E. et al., 1995, Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study. BMJ, 310, 970–973.
  • PACKER, L., RIMBACH, G., and VIRGILI, F., 1999, Antioxidant activity and biologic properties of a procyanidin-rich extract from pine (Pinus maritima) bark, pycnogenol. Free Radical Biology and Medicine, 27, 704–724.
  • PALSSON, S., AEVARSSON, O., and SKOOG, I., 1999, Depression, cerebral atrophy, cognitive performance and incidence of dementia. Population study of 85-year-olds. British Journal of Psychiatry, 174, 249–253.
  • PAPPOLLA, M. A., CHYAN, Y. J., POEGGELER, B., FRANGIONE, B., WILSON, G., OHISO, J. et al., 2000, An assessment of the antioxidant and the antiamyloidogenic properties of melatonin: implications for Alzheimer's disease. Journal of Neural Transmission ( Budapest), 107, 203–231.
  • PASINETTI, G. M., 2002, From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer's disease: the role of NSAIDs and cyclooxygenase in beta-amyloidosis and clinical dementia. Journal of Alzheimer's Disease, 4, 435–445.
  • PENG, Q. L., BUZ'ZARD, A. R., and LAU, B. H., 2002, Pycnogenol protects neurons from amyloid-beta peptide-induced apoptosis. Brain Research. Molecular Brain Research, 104, 55–65.
  • PERRY, E. K., PERRY, R. H., and TOMLINSON, B. E., 1982, The influence of agonal status on some neurochemical activities of postmortem human brain tissue. Neuroscience Letters, 29, 303–307.
  • PERRY, G., RAINA, A. K., NUNOMURA, A., WATAYA, T., SAYRE, L. M., and SMITH, M. A., 2000, How important is oxidative damage? Lessons from Alzheimer's disease. Free Radical Biology and Medicine, 28, 831–834.
  • PETANCESKA, S. S., NAGY, V., FRAIL, D., and GANDY, S., 2000, Ovariectomy and 17beta-estradiol modulate the levels of Alzheimer's amyloid beta peptides in brain. Neurology, 54, 2212–2217.
  • PIKE, C. J., WALENCEWICZ, A. J., OLABE, C. G., and COTMAN, C. W., 1991, In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity. Brain Research, 563, 311–314.
  • PIKE, C. J., BURDICK, D., WALENCEWICZ, A. J., OLABE, C. G., and COTMAN, C. W., 1993, Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. Journal of Neuroscience, 13, 1676–1687.
  • PILLOT, T., ODETHALS, M., VANLOO, B., TALUSSOT, C., BRASSEUR, R., VANDEKERCICHOVE, J. et al., 1996, Fusogenic properties of the C-terminal domain of the Alzheimer beta-amyloid peptide. Journal of Biological Chemistry, 271, 28757–28765.
  • POLYAK, K., XIA, Y., ZWEIER, J. L., KINZLER, K. W., and VOGELSTEIN, B., 1997, A model for p53-induced apoptosis. Nature, 389, 300–305.
  • PRATICO, D., 2002, Alzheimer's disease and oxygen radicals: new insights. Biochemical Pharmacology, 63, 563–567.
  • PRATICO, D., TANGIRALA, R. K., RADER, D. J., ROKACH, J., and FITZGERALD, G. A., 1998, Vitamin E suppresses isoprostane generation in vivo and reduces atherosclerosis in ApoE-deficient mice. Nature Medicine, 4, 1189–1192.
  • PRATICO, D., URYU, K., LEIGHT, S., TROJANOSWKI, J. Q., LEE, V. M., 2001, Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. Journal of Neuroscience, 21, 4183–4187.
  • PRELLI, F., CASTANO, E., OLENNER, G. G., and FRANGIONE, B., 1988, Differences between vascular and plaque core amyloid in Alzheimer's disease. Journal of Neurochemistry, 51, 648–651.
  • PRYOR, W. A., 1982, Free radical biology: xenobiotics, cancer, and aging. Annals of the New York Academy of Sciences, 393, 1–22.
  • PRYOR, W. A., 1986, Oxy-radicals and related species: their formation, lifetimes, and reactions. Annual Review of Physiology, 48, 657–667.
  • PUTTAPARTHI, K., GITOMER, W. L., KRISHNAN, U., SON, M., RAJENDRAN, B., and ELLIOTT, J. L., 2002, Disease progression in a transgenic model of familial amyotrophic lateral sclerosis is dependent on both neuronal and non-neuronal zinc binding proteins. Journal of Neuroscience, 22, 8790–8796.
  • PUERFURTH, H. W., WIJSMAN, E. M., ST GEORGE-HYSLOP, P. H., and SELKOE, D. J., 1995, Beta APP mRNA transcription is increased in cultured fibroblasts from the familial Alzheimer's disease-1 family. Brain Research. Molecular Brain Research, 28, 319–337.
  • RASMUSSON, D. X., BRANDT, J., MARTIN, D. B., and FOLSTEIN, M. F., 1995, Head injury as a risk factor in Alzheimer's disease. Brain Injury, 9, 213–219.
  • REBECK, G. W., REITER, J. S., STRICKLAND, D. K. and HYMAN, B. T., 1993, Apolipoprotein e in sporadic alzheimer's disease: Allelic variation and receptor interactions. Neuron, 11, 575–580.
  • REILLY, C. A., and AUST, S. D., 1997, Stimulation of the ferroxidase activity of ceruloplasmin during iron loading into ferritin. Archives of Biochemistry and Biophysics, 347, 242–248.
  • REITER, R. J., 1998, Oxidative damage in the central nervous system: protection by melatonin. Progress in Neurobiology, 56, 359–384.
  • ROHER, A. E., BALL, M. J., BHAVE, S. V., and WAKADE, A. R., 1991a, Beta-amyloid from Alzheimer disease brains inhibits sprouting and survival of sympathetic neurons. Biochemical and Biophysical Research Communications, 174, 572–579.
  • ROHER, A. E., PALMER, K. C., CAPODILUPO, J., WAKADE, A. R., and BALL, M. J., 1991b, New biochem-ical insights to unravel the pathogenesis of Alzheimer's lesions. Canadian Journal of Neurological Sciences, 18, 408–410.
  • ROMANO, C., PETTINATO, R., RAGUSA, L., BARONE, C., ALBERTI, A., and FAILLA, P., 2002, Is there a relationship between zinc and the peculiar comorbidities of Down syndrome? Down's Syndrome. Research and Practice, 8, 25–28.
  • RYDEN, L., and EAKER, D., 1983, Identification of the thiol groups in human ceruloplasmin. European Journal of Biochemistry, 132, 241–247.
  • SANO, M., ERNESTO, C., THOMAS, R. G., KLAUBER, M. R., SCHAFER, K., GRUNDMAN, M. et al., 1997, A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's disease cooperative study [see comments]. New England Journal of Medicine, 336, 1216–1222.
  • SAYRE, L. M., ZELASKO, D. A., HARRIS, P. L., PERRY, G., SALOMON, R. G., and SMITH, M. A., 1997, 4-hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. Journal of Neurochemistry, 68, 2092–2097.
  • SCHAFER, F. Q., and BUETTNER, G. R., 2000, Acidic pH amplifies iron-mediated lipid peroxidation in cells. Free Radical Biology and Medicine, 28, 1175–1181.
  • SCHEUNER, D., ECKMAN, C., JENSEN, M., SONG, X., CITRON, M., SUZUKI, N. et al., 1996, Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nature Medicine, 2, 864–870.
  • SCHUBERT, D., and CHEVION, M., 1995, The role of iron in beta amyloid toxicity. Biochemical and Biophysical Research Communications, 216, 702–707.
  • SELKOE, D. J., 1996, Cell biology of the beta-amyloid precursor protein and the genetics of Alzheimer's disease. Cold Spring Harbour Symposia on Quantitative Biology, 61, 587–596.
  • SHEARMAN, M. S., RAGAN, C. I., and IVERSEN, L. L., 1994, Inhibition of PC12 cell redox activity is a specific, early indicator of the mechanism of beta-amyloid-mediated cell death. Proceedings of the National Academy of Sciences USA, 91, 1470–1474.
  • SHERRINGTON, R., ROGAEV, E. I., LIANG, Y., ROGAEVA, E. A., LEVESQUE, G., IKEDA, M. et al., 1995, Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature, 375, 754–760.
  • SIMMONS, L. K., MAY, P. C., TOMASELLI, K. J., RYDEL, R. E., FUSON, K. S., BRIGHAM, E. F. et al., 1994, Secondary structure of amyloid beta peptide correlates with neurotoxic activity in vitro. Molecular Pharmacology, 45, 373–379.
  • SIMONS, M., KELLER, P., DE STROOPER, B., BEYREUTHER, K., DOTTI, C. G., and SIMONS, K., 1998, Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proceedings of the National Academy of Sciences USA, 95, 6460–6464.
  • SIMPKINS, J. W., GREEN, P. S., GRIDLEY, K. E., SINGH, M., DE FIEBRE, N. C., and RAJAKUMAR, G., 1997, Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer's disease. American Journal of Medicine, 103, 19S–25S.
  • SIMPSON, I. A., CHUNDU, K. R., DAVIES-HILL, T., HONER, W. G., and DAVIES, P., 1994, Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Annals of Neurology, 35, 546–551.
  • SKOOG, I., 1998, A review on blood pressure and ischaemic white matter lesions. Dementia and Geriatric Cognitive Disorders, 9, 13–19.
  • SMITH, C., MITCHINSON, M. J., ARUOMA, O. I. and HALLIWELL, B., 1992, Stimulation of lipid peroxida-tion and hydroxyl-radical generation by the contents of human atherosclerotic lesions. Biochem J, 286, 901–905.
  • SMITH, M. A., and PERRY, G., 1997a, The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis. Journal of Neuropathology and Experimental Neurology, 56, 217.
  • SMITH, M. A., and PERRY, G., 1997b, Oxidative stress is central to the pathogenesis of Alzheimer disease (Alzheimer's International Internet Conference). http://www.a/zforum.org/res/for/perryl/ Oxstress.asp
  • SMITH, M. A., KUTTY, R. K., RICHEY, P. L., YAN, S. D., STERN, D., CHADER, G. J. et al., 1994a, Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. American Journal of Pathology, 145, 42–47.
  • SMITH, M. A., RICHEY, P. L., TANEDA, S., KUTTY, R. K., SAYRE, L. M., MONNIER, V. M. et al., 1994b, Advanced Maillard reaction end products, free radicals, and protein oxidation in Alzheimer's disease. Annals of the New York Academy of Sciences, 738, 447–454.
  • SMITH, M. A., RUDNICKA-NAWROT, M., RICHEY, P. L., PRAPROTNIK, D., MULVIHILL, P., MILLER, C. A. et al., 1995a, Carbonyl-related post-translational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer's disease. Journal of Neurochemistry, 64, 2660–2666.
  • SMITH, M. A., Sayre, L. M., MONNIER, V. M. and Perry, G., 1995c, Radical ageing in alzheimer's disease. Trends in Neurosciences, 18, 172–176.
  • SMITH, M. A., SAYRE, L. M., VITEK, M. P., MONNIER, V. M., and PERRY, G., 1995b, Early ageing and Alzheimer's. Nature, 374, 316.
  • SMITH, M. A., PERRY, G., RICHEY, P. L., SAYRE, L. M., ANDERSON, V. E., BEAL, M. F. et al., 1996a, Oxidative damage in Alzheimer's. Nature, 382, 120–121.
  • SMITH, M. A., SIEDLAK, S. L., RICHEY, P. L., NAGARAJ, R. H., ELHAMMER, A., and PERRY, G., 1996b, Quantitative solubilization and analysis of insoluble paired helical filaments from Alzheimer disease. Brain Research, 717, 99–108.
  • SMITH, M. A., HARRIS, P. L., SAYRE, L. M., and PERRY, G., 1997a, Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proceedings of the National Academy of Sciences USA, 94, 9866–9868.
  • SMITH, M. A., RICHEY HARRIS, P. L., SAYRE, L. M., BECKMAN, J. S., and PERRY, G., 1997b, Widespread peroxynitrite-mediated damage in Alzheimer's disease. Journal of Neuroscience, 17, 2653–2657.
  • SMITH, M. A., CASADESUS, G., JOSEPH, J. A., and PERRY, G., 2002, Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain. Free Radical Biology and Medicine, 33, 1194–1199.
  • SOUTHORN, P. A., and Pow's, G., 1988a, Free radicals in medicine. I. Chemical nature and biologic reactions. Mayo Clinic Proceedings, 63, 381–389.
  • SOUTHORN, P. A., and Pow's, G., 1988b, Free radicals in medicine. II. Involvement in human disease. Mayo Clinic Proceedings, 63, 390–408.
  • SPARKS, D. L., HUNSAKER, J. C., III, SCHEFF, S. W., KRYSCIO, R. J., HENSON, J. L., and MARKESBERY, W. R., 1990, Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease. Neurobiology of Aging, 11, 601–607.
  • STRITTMATTER, W. J., SAUNDERS, A. M., SCHMECHEL, D., PERICAK-VANCE, M., ENGHILD, J., SALVESEN, G. S. et al., 1993, Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Sciences USA, 90, 1977–1981.
  • STUDER, R., BAYSANG, G., and BRACK, C., 2001, N-Acetyl-L-cystein downregulates beta-amyloid precursor protein gene transcription in human neuroblastoma cells. Biogerontology, 2, 55–60.
  • SU, Y., and CHANG, P. T., 2001, Acidic pH promotes the formation of toxic fibrils from beta-amyloid peptide. Brain Research, 893, 287–291.
  • SULKAVA, R., 1998, Anti-inflammatory drug therapy for prevention of Alzheimer's disease? Duodecim, 114, 2025–2027.
  • SUZUKI, N., CHEUNG, T. T., CAI, X. D., ODAKA, A., OTVOS, L., JR, ECKMAN, C. et al., 1994, An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science, 264, 1336–1340.
  • TANZI, R. E., GUSELLA, J. F., WATKINS, P. C., BRUNS, G. A., ST GEORGE-HYSLOP, P., VAN KEUREN, M. L. et al., 1987, Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science, 235, 880–884.
  • TANZI, R. E., MCCLATCHEY, A. I., LAMPERTI, E. D., VILLA-KOMAROFF, L., GUSELLA, J. F., and NEVE, R. L., 1988, Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature, 331, 528–530.
  • TATEMICHI, M., NAGATA, H., SEKIZUKA, E., MORISHITA, T., MIYAIRI, M., TSUCHIYA, M. et al., 1996, Differences in hemostasis among sclerosing agents in endoscopic injection sclerotherapy. Digestive Diseases and Sciences, 41, 562–570.
  • TELLER, J. K., Russo, C., DEBUSK, L. M., ANGELINI, G., ZACCHEO, D., DAGNA-BRICARELLI, F. et al., 1996, Presence of soluble amyloid beta-peptide precedes amyloid plaque formation in Down's syndrome. Nature Medicine, 2, 93–95.
  • THOMAS, T., THOMAS, G., MCLENDON, C., SUTTON, T., and MULLAN, M., 1996, Beta-amyloid-mediated vasoactivity and vascular endothelial damage. Nature, 380, 168–171.
  • TORSDOTTIR, G., KRISTINSSON, J., SVEINBJORNSDOTTIR, S., SNAEDAL, J., and JOHANNESSON, T., 1999, Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Pharmacology and Toxicology, 85, 239–243.
  • UCHIDA, S., EDAMATSU, R., HIRAMATSU, M., MORI, A., NONAKA, G., NISHIOKA, I. et al., 1987, Condensed tannins scavenge active oxygen free radicals. Medical Science Research, 15, 831–832.
  • VARADARAJAN, S., YATIN, S., AKSENOVA, M., and BUTTERFIELD, D. A., 2000, Review: Alzheimer's amyloid beta-peptide-associated free radical oxidative stress and neurotoxicity. Journal of Structural Biology, 130, 184–208.
  • VEURINK, G., Liu, D., TADDEI, K., PERRY, G., SMITH, M. A., ROBERTSON, T. A. et al., 2003, Reduction of inclusion body pathology in ApoE-deficient mice fed a combination of antioxidants. Free Radical Biology and Medicine, 34, 1070–1077.
  • VINCENT, B., and SMITH, J. D., 2000, Effect of estradiol on neuronal Swedish-mutated beta-amyloid precursor protein metabolism: reversal by astrocytic cells. Biochemical and Biophysical Research Communications, 271, 82–85.
  • VOLICER, L., and CRINO, P. B., 1990, Involvement of free radicals in dementia of the Alzheimer type: a hypothesis. Neurobiology of Aging, 11, 567–571.
  • WADDINGTON, E., CROFT, K., CLARNETTE, R., MORI, T., and MARTINS, R., 1999, Plasma F2-isoprostane levels are increased in Alzheimer's disease: evidence of increased oxidative stress in vivo. Alzheimer's Reports, 2, 277–282.
  • WALKER, D. G., LUE, L. F., and BEACH, T. G., 2002, Increased expression of the urokinase plasminogen-activator receptor in amyloid beta peptide-treated human brain microglia and in AD brains. Brain Research, 926, 69–79.
  • WESTBROOK, G. L., and MAYER, M. L., 1987, Micromolar concentrations of Zn2± antagonise NMDA and GABA responses of hippocampal neurons. Nature, 328, 640–643.
  • WETTSTEIN, A., 2000, Cholinesterase inhibitors and gingko extracts-are they comparable in the treat-ment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months' duration. Phytomedicine, 6, 393–401.
  • WHITE, L. R., PETROVITCH, H., Ross, G. W., MASAKI, K., IZMURLIAN, G., FOLEY, D. et al., 1998, Rates, characteristics, and risk factors for dementia among Japanese-American men in Honolulu Comparisons with other Japanese- and European-ancestry populations. Neurobiology of Aging, 19 (Suppl. 4), S200.
  • WHITSON, J. S., SELKOE, D. J., and COTMAN, C. W., 1989, Amyloid beta protein enhances the survival of hippocampal neurons in vitro. Science, 243, 1488–1490.
  • WILLS, E. D., 1965, Mechanisms of lipid peroxide formation in tissues. Role of metals and haematin proteins in the catalysis of the oxidation of unsaturated fatty acids. Biochimica et Biophysica Acta, 98, 238–251.
  • WILLS, E. D., 1966, Mechanisms of lipid peroxide formation in animal tissues. Biochemical Journal, 99, 667–676.
  • WINTHER, K., RANDLOV, C., REIN, E., and MEHLSEN, J., 1998, Effects of ginkgo biloba extract 011 cognitive function and blood pressure in elderly subjects. Current Therapeutic Research, Clinical and Experimental, 59, 881–888.
  • WISNIEWSKI, K. E., LAURE-KAMIONOWSKA, M., and WISNIEWSKI, H. M., 1984, Evidence of arrest of neurogenesis and synaptogenesis in brains of patients with Down's syndrome. New England Journal of Medicine, 311, 1187–1188.
  • WISNIEWSKI, K. E., WISNIEWSKI, H. M., and WEN, G. Y., 1985, Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome. Annals of Neurology, 17, 278–282.
  • WISNIEWSKI, T., LALOWSKI, M., LEVY, E., MARQUES, M. R., and FRANGIONE, B., 1994, The amino acid sequence of neuritic plaque amyloid from a familial Alzheimer's disease patient. Annals of Neurology, 35, 245–246.
  • WISNIEWSKI, T., GHISO, J., and FRANGIONE, B., 1997, Biology of A beta amyloid in Alzheimer's disease. Neurobiology of Disease, 4, 313–328.
  • XIE, L., HELMERHORST, E., TADDEI, K., PLEWRIGHT, B., VAN BRONSWIJK, W., and MARTINS, R., 2002, Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor. Journal of Neuroscience, 22, RC221.
  • XU, H., GOURAS, G.K., GREENFIELD, J. P., VINCENT, B., NASLUND, J., MAZZARELLI, L. et al., 1998, Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides. Nature Medicine, 4, 447–451.
  • YAMAGUCHI, H., SUGIHARA, S., OGAWA, A., OSHIMA, N., and IHARA, Y., 2001, Alzheimer beta amyloid deposition enhanced by ApoE epsilon4 gene precedes neurofibrillary pathology in the frontal association cortex of nondemented senior subjects. Journal of Neuropathology and Experimental Neurology, 60, 731–739.
  • YANG, D. S., SMITH, J. D., ZHOU, Z., GANDY, S. E., and MARTINS, R. N., 1997, Characterization of the binding of amyloid-beta peptide to cell culture-derived native apolipoprotein E2, E3, and E4 iso-forms and to isoforms from human plasma. Journal of Neurochemistry, 68, 721–725.
  • YANKNER, B. A., 1996, Mechanisms of neuronal degeneration in Alzheimer's disease. Neuron, 16, 921–932.
  • YANKNER, B. A., CACERES, A., and DUFFY, L. K., 1990a, Nerve growth factor potentiates the neurotoxi- city of beta amyloid. Proceedings of the National Academy of Sciences USA, 87, 9020–9023.
  • YANKNER, B. A., DUFFY, L. K., and KIRSCHNER, D. A., 1990b, Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science, 250, 279–282.
  • YANKNER, B. A., DAWES, L. R., FISHER, S., VILLA-KOMAROFF, L., OSTER-GRANITE, M. L., and NEVE, R. L., 1989, Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science, 245, 417–420.
  • YATES, C. M., BUTTERWORTH, J., TENNANT, M. C., and GORDON, A., 1990, Enzyme activities in relation to pH and lactate in postmortem brain in Alzheimer-type and other dementias. Journal of Neurochemistry, 55, 1624–1630.
  • YOSHIKAWA, K., AIZAWA, T., and HAYASHI, Y., 1992, Degeneration in vitro of post-mitotic neurons overexpressing the Alzheimer amyloid protein precursor. Nature, 359, 64–67.
  • ZAMZAMI, N., HIRSCH, T., DALLAPORTA, B., PETIT, P. X., and KROEMER, G., 1997, Mitochondrial implication in accidental and programmed cell death: apoptosis and necrosis. Journal of Bioenergetics and Biomembranes, 29, 185–193.
  • ZHANG, P., Liu, B., KANG, S. W., SEO, M. S., RHEE, S. G., and OBEID, L. M., 1997, Thioredoxin peroxidase is a novel inhibitor of apoptosis with a mechanism distinct from that of Bc1-2. Journal of Biological Chemistry, 272, 30615–30618.
  • ZUU, H., Guo, Q., and MATTSON, M. P., 1999, Dietary restriction protects hippocampal neurons against the death-promoting action of a presenilin-1 mutation. Brain Research, 842, 224–229.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.