Skip to main content
SpringerLink
Log in

The Potential Application of Antioxidant Agents in Alzheimer Disease Therapeutics

  • Chapter
Book cover Pharmacological Mechanisms in Alzheimer's Therapeutics

  • 698 Accesses

Oxidative stress is a fundamental process contributing to the neuronal degeneration and death observed in Alzheimer disease, and many studies using markers of oxidative damage have provided evidence supporting this hypothesis. Consequently, antioxidants that prevent the detrimental consequences of oxidative stress are considered to be a promising approach to neuroprotection. While the clinical value of antioxidants for the prevention of AD is currently ambiguous, they still appear to be the most promising weapons that can be developed against disease progression.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Atwood, C. S., Huang, X., Moir, R. D., Tanzi, R. E., & Bush, A. I. (1999). Role of free radicals and metal ions in the pathogenesis of Alzheimer's disease. Metal Ions in Biological Systems, 36, 309–364.

    PubMed  CAS  Google Scholar 

  • 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 physiological acidosis. The Journal of Biological Chemistry, 273, 12817–12826.

    Article  PubMed  CAS  Google Scholar 

  • Bayer, T. A., Schafer, S., Simons, A., Kemmling, A., Kamer, T., Tepest, R., et al. (2003). Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice. Proceedings of the National Academy of Sciences of the United States of America, 100, 14187–14192.

    Article  PubMed  CAS  Google Scholar 

  • Bianchetti, A., Rozzini, R., & Trabucchi, M. (2003). Effects of acetyl-L-carnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors. Current Medical Research and Opinion, 19, 350–353.

    Article  PubMed  CAS  Google Scholar 

  • Bosetti, F., Brizzi, F., Barogi, S., Mancuso, M., Siciliano, G., Tendi, E. A., et al. (2002). Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease. Neurobiology of Aging, 23, 371–376.

    Article  PubMed  CAS  Google Scholar 

  • Bubber, P., Haroutunian, V., Fisch, G., Blass, J. P., & Gibson, G. E. (2005). Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications. Annals of Neurology, 57, 695–703.

    Article  PubMed  CAS  Google Scholar 

  • Bush, A. I. (2003). The metallobiology of Alzheimer's disease. Trends in Neurosciences, 26, 207–214.

    Article  PubMed  CAS  Google Scholar 

  • Bush, A. I., Pettingell, W. H., Multhaup, G., d Paradis, M., Vonsattel, J. P., Gusella, J. F., et al. (1994). Rapid induction of Alzheimer A beta amyloid formation by zinc. Science, 265, 1464–1467.

    Article  PubMed  CAS  Google Scholar 

  • Bush, A. I., Pettingell, W. H., Jr., Paradis, M. D., & Tanzi, R. E. (1994). Modulation of A beta adhesiveness and secretase site cleavage by zinc. The Journal of Biological Chemistry, 269, 12152–12158.

    PubMed  CAS  Google Scholar 

  • Cardoso, S. M., Proenca, M. T., Santos, S., Santana, I., & Oliveira, C. R. (2004). Cytochrome c oxidase is decreased in Alzheimer's disease platelets. Neurobiology of Aging, 25, 105–110.

    Article  PubMed  CAS  Google Scholar 

  • Castellani, R., Hirai, K., Aliev, G., Drew, K. L., Nunomura, A., Takeda, A., et al. (2002). Role of mitochondrial dysfunction in Alzheimer's disease. Journal of Neuroscience Research, 70, 357–360.

    Article  PubMed  CAS  Google Scholar 

  • Cherny, R. A., Atwood, C. S., Xilinas, M. E., Gray, D. N., Jones, W. D., McLean, C. A., et al. (2001). Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron, 30, 665–676.

    Article  PubMed  CAS  Google Scholar 

  • Connor, J. R., Milward, E. A., Moalem, S., Sampietro, M., Boyer, P., Percy, M. E., et al. (2001). Is hemochromatosis a risk factor for Alzheimer's disease? Journal of Alzheimer's Disease, 3, 471–477.

    PubMed  CAS  Google Scholar 

  • Cottrell, D. A., Borthwick, G. M., Johnson, M. A., Ince, P. G., & Turnbull, D. M. (2002). The role of cytochrome c oxidase deficient hippocampal neurones in Alzheimer's disease. Neuropathology and Applied Neurobiology, 28, 390–396.

    Article  PubMed  CAS  Google Scholar 

  • Dong, J., Atwood, C. S., Anderson, V. E., Siedlak, S. L., Smith, M. A., Perry, G., et al. (2003). Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry, 42, 2768–2773.

    Article  PubMed  CAS  Google Scholar 

  • Engelhart, M. J., Geerlings, M. I., Ruitenberg, A., van Swieten, J. C., Hofman, A., Witteman, J. C., et al. (2002). Dietary intake of antioxidants and risk of Alzheimer disease. The Journal of the American Medical Association, 287, 3223–3229.

    Article  CAS  Google Scholar 

  • Frolich, L., Gotz, M. E., Weinmuller, M., Youdim, M. B., Barth, N., Dirr, A., et al. (2004). (r)-, but not (s)-alpha lipoic acid stimulates deficient brain pyruvate dehydrogenase complex in vascular dementia, but not in Alzheimer dementia. Journal of Neural Transmission, 111, 295–310.

    Article  PubMed  CAS  Google Scholar 

  • Gibson, G. E., Park, L. C., Sheu, K. F., Blass, J. P., & Calingasan, N. Y. (2000). The alpha-ketoglutarate dehydrogenase complex in neurodegeneration. Neurochemistry International, 36, 97–112.

    Article  PubMed  CAS  Google Scholar 

  • Grundman, M. (2000). Vitamin E and Alzheimer disease: the basis for additional clinical trials. The American Journal of Clinical Nutrition, 71, 630S–636S.

    PubMed  CAS  Google Scholar 

  • Gutzmann, H., & Hadler, D. (1998). Sustained efficacy and safety of idebenone in the treatment of Alzheimer's disease: Update on a 2-year double-blind multicentre study. Journal of Neural Transmission. Supplementum, 54, 301–310.

    PubMed  CAS  Google Scholar 

  • Gutzmann, H., Kuhl, K. P., Hadler, D., & Rapp, M. A. (2002). Safety and efficacy of idebenone versus tacrine in patients with Alzheimer's disease: Results of a randomized, double-blind, parallel-group multicenter study. Pharmacopsychiatry, 35, 12–18.

    Article  PubMed  CAS  Google Scholar 

  • Hagen, T. M., Ingersoll, R. T., Lykkesfeldt, J., Liu, J., Wehr, C. M., Vinarsky, V., et al. (1999). (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. The FASEB Journal, 13, 411–418.

    PubMed  CAS  Google Scholar 

  • Hager, K., Marahrens, A., Kenklies, M., Riederer, P., & Munch, G. (2001). Alpha-lipoic acid as a new treatment option for Azheimer type dementia. Archives of Gerontology and Geriatrics, 32, 275–282.

    Article  PubMed  CAS  Google Scholar 

  • Hebert, L. E., Scherr, P. A., Bienias, J. L., Bennett, D. A., & Evans, D. A. (2003). Alzheimer disease in the US population: Prevalence estimates using the 2000 census. Archives of Neurology, 60, 1119–1122.

    Article  PubMed  Google Scholar 

  • 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 Research, 21, 3017–3023.

    CAS  Google Scholar 

  • Honda, K., Casadesus, G., Petersen, R. B., Perry, G., & Smith, M. A. (2004). Oxidative stress and redox-active iron in Alzheimer's disease. Annals of the New York Academy of Sciences, 1012, 179–182.

    Article  PubMed  CAS  Google Scholar 

  • Huang, X., Atwood, C. S., Hartshorn, M. A., Multhaup, G., Goldstein, L. E., Scarpa, R. C., et al. (1999). The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry, 38, 7609–7616.

    Article  PubMed  CAS  Google Scholar 

  • Huang, X., Cuajungco, M. P., Atwood, C. S., Hartshorn, M. A., Tyndall, J. D., Hanson, G. R., et al. (1999). Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. The Journal of Biological Chemistry, 274, 37111–37116.

    Article  PubMed  CAS  Google Scholar 

  • Hudson, S., & Tabet, N. (2003). Acetyl-L-carnitine for dementia. Cochrane Database of Systematic Reviews, CD003158.

    Google Scholar 

  • Jesudason, E. P., Masilamoni, J. G., Jesudoss, K. S., & Jayakumar, R. (2005). The protective role of DL-alpha-lipoic acid in the oxidative vulnerability triggered by Abeta-amyloid vaccination in mice. Molecular and Cellular Biochemistry, 270, 29–37.

    Article  PubMed  CAS  Google Scholar 

  • Keyse, S. M., & Tyrrell, R. M. (1989). Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proceedings of the National Academy of Sciences of the United States of America, 86, 99–103.

    Article  PubMed  CAS  Google Scholar 

  • Khachaturian, Z. S. (1985). Diagnosis of Alzheimer's disease. Archives of Neurology, 42, 1097–1105.

    PubMed  CAS  Google Scholar 

  • Kumar, U., Dunlop, D. M., & Richardson, J. S. (1994). Mitochondria from Alzheimer's fibroblasts show decreased uptake of calcium and increased sensitivity to free radicals. Life Sciences, 54, 1855–1860.

    Article  PubMed  CAS  Google Scholar 

  • Laurin, D., Masaki, K. H., Foley, D. J., White, L. R., & Launer, L. J. (2004). Midlife dietary intake of antioxidants and risk of late-life incident dementia: The Honolulu-Asia Aging Study. American Journal of Epidemiology, 159, 959–967.

    Article  PubMed  Google Scholar 

  • Le Bars, P. L., Katz, M. M., Berman, N., Itil, T. M., Freedman, A. M., & Schatzberg, A. F. (1997). A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. The Journal of the American Medical Association, 278, 1327–1332.

    Article  CAS  Google Scholar 

  • Liu, G., Garrett, M. R., Men, P., Zhu, X., Perry, G., & Smith, M. A. (2005). Nanoparticle and other metal chelation therapeutics in Alzheimer disease. Biochimica et Biophysica Acta, 1741, 246–252.

    PubMed  CAS  Google Scholar 

  • Lovell, M. A., Robertson, J. D., Teesdale, W. J., Campbell, J. L., & Markesbery, W. R. (1998). Copper, iron and zinc in Alzheimer's disease senile plaques. Journal of the Neurological Sciences, 158, 47–52.

    Article  PubMed  CAS  Google Scholar 

  • Luchsinger, J. A., Tang, M. X., Shea, S., & Mayeux, R. (2003). Antioxidant vitamin intake and risk of Alzheimer disease. Archives of Neurology, 60, 203–208.

    Article  PubMed  Google Scholar 

  • Martinez-Cano, E., Ortiz-Genaro, G., Pacheco-Moises, F., Macias-Islas, M. A., Sanchez-Nieto, S., & Rosales-Corral, S. A. (2005). [Functional disorders of FOF1-ATPase in submitochondrial particles obtained from platelets of patients with a diagnosis of probable Alzheimer's disease]. Revista de Neurologia, 40, 81–85.

    PubMed  CAS  Google Scholar 

  • May, P. M., & Bulman, R. A. (1983). The present status of chelating agents in medicine. Progress in Medicinal Chemistry, 20, 225–336.

    Article  PubMed  CAS  Google Scholar 

  • McLachlan, D. R., Smith, W. L., & Kruck, T. P. (1993). Desferrioxamine and Alzheimer's disease: Video home behavior assessment of clinical course and measures of brain aluminum. Therapeutic Drug Monitoring, 15, 602–607.

    PubMed  CAS  Google Scholar 

  • Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., et al. (1991). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology, 41, 479–486.

    PubMed  CAS  Google Scholar 

  • Montgomery, S. A., Thal, L. J., & Amrein, R. (2003). Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. International Clinical Psychopharmacology, 18, 61–71.

    Article  PubMed  Google Scholar 

  • Moreira, P. I., Honda, K., Zhu, X., Nunomura, A., Casadesus, G., Smith, M. A., & Perry, G. (2006). Brain and brawn: Parallels in oxidative strength. Neurology, 66, S97–S101.

    Article  PubMed  CAS  Google Scholar 

  • Moreira, P. I., Smith, M. A., Zhu, X., Santos, M. S., Oliveira, C. R., & Perry, G. (2004). Therapeutic potential of oxidant mechanisms in Alzheimer disease. Expert Reviews in Neurotherapeutics, 4, 995–1004.

    Article  CAS  Google Scholar 

  • 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. The Journal of the American Medical Association, 287, 3230–3237.

    Article  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Nunomura, A., Perry, G., Pappolla, M. A., Wade, R., Hirai, K., Chiba, S., et al. (1999). RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. Journal of Neuroscience Research, 19, 1959–1964.

    CAS  Google Scholar 

  • Ojaimi, J., Masters, C. L., McLean, C., Opeskin, K., McKelvie, P., & Byrne, E. (1999). Irregular distribution of cytochrome c oxidase protein subunits in aging and Alzheimer's disease. Annals of Neurology, 46, 656–660.

    Article  PubMed  CAS  Google Scholar 

  • Opazo, C., Huang, X., Cherny, R. A., Moir, R. D., Roher, A. E., White, A. R., et al. (2002). Metalloenzyme-like activity of Alzheimer's disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2) O(2). The Journal of Biological Chemistry, 277, 40302–40308.

    Article  PubMed  CAS  Google Scholar 

  • Packer, L., Tritschler, H. J., & Wessel, K. (1997). Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radical Biology & Medicine, 22, 359–378.

    Article  CAS  Google Scholar 

  • Perry, G., Nunomura, A., Hirai, K., Zhu, X., Perez, M., Avila, J., et al. (2002). Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases? Free Radical Biology and Medicine, 33, 1475–1479.

    Article  PubMed  CAS  Google Scholar 

  • Petersen, R. C., Thomas, R. G., Grundman, M., Bennett, D., Doody, R., Ferris, S., et al. (2005). Vitamin E and donepezil for the treatment of mild cognitive impairment. The New England Journal of Medicine, 352, 2379–2388.

    Article  PubMed  CAS  Google Scholar 

  • Premkumar, D. R., Smith, M. A., Richey, P. L., Petersen, R. B., Castellani, R., Kutty, R. K., et al. (1995). Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer's disease. Journal of Neurochemistry, 65, 1399–1402.

    PubMed  CAS  Google Scholar 

  • Ritchie, C. W., Bush, A. I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., et al. (2003). Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Archives of Neurology, 60, 1685–1691.

    Article  PubMed  Google Scholar 

  • Rottkamp, C. A., Raina, A. K., Zhu, X., Gaier, E., Bush, A. I., Atwood, C. S., et al. (2001). Redox-active iron mediates amyloid-beta toxicity. Free Radical Biology and Medicine, 30, 447–450.

    Article  PubMed  CAS  Google Scholar 

  • 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. The New England Journal of Medicine, 336, 1216–1222.

    Article  PubMed  CAS  Google Scholar 

  • Savory, J., Huang, Y., Wills, M. R., & Herman, M. M. (1998). Reversal by desferrioxamine of tau protein aggregates following two days of treatment in aluminum-induced neurofibrillary degeneration in rabbit: Implications for clinical trials in Alzheimer's disease. Neurotoxicology, 19, 209–214.

    PubMed  CAS  Google Scholar 

  • Sayre, L. M., Perry, G., Harris, P. L., Liu, Y., Schubert, K. A., & Smith, M. A. (2000). In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: A central role for bound transition metals. Journal of Neurochemistry, 74, 270–279.

    Article  PubMed  CAS  Google Scholar 

  • Sayre, L. M., Zelasko, D. A., Harris, P. L., Perry, G., Salomon, R. G., & Smith, M. A. (1997). 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. Journal of Neurochemistry, 68, 2092–2097.

    Article  PubMed  CAS  Google Scholar 

  • Scarmeas, N., Stern, Y., Tang, M. X., Mayeux, R., & Luchsinger, J. A. (2006). Mediterranean diet and risk for Alzheimer's disease. Annals of Neurology, 59, 912–921.

    Article  PubMed  Google Scholar 

  • Sheu, K. F., Kim, Y. T., Blass, J. P., & Weksler, M. E. (1985). An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain. Annals of Neurology, 17, 444–449.

    Article  PubMed  CAS  Google Scholar 

  • Smith, M. A., Harris, P. L., Sayre, L. M., & Perry, G. (1997). Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proceedings of the National Academy of Sciences of the United States of America, 94, 9866–9868.

    Article  PubMed  CAS  Google Scholar 

  • Smith, M. A., Kutty, R. K., Richey, P. L., Yan, S. D., Stern, D., Chader, G. J., et al. (1994). Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. The American Journal of Pathology, 145, 42–47.

    PubMed  CAS  Google Scholar 

  • Smith, M. A., Nunomura, A., Lee, H. G., Zhu, X., Moreira, P. I., Avila, J., et al. (2005). Chronological primacy of oxidative stress in Alzheimer disease. Neurobiology of Aging, 26, 579–580; discussion 587–595.

    Article  PubMed  CAS  Google Scholar 

  • Smith, M. A., Perry, G., Richey, P. L., Sayre, L. M., Anderson, V. E., Beal, M. F., et al. (1996). Oxidative damage in Alzheimer's. Nature, 382, 120–121.

    Article  PubMed  CAS  Google Scholar 

  • Sparks, D. L., & Schreurs, B. G. (2003). Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America, 100, 11065–11069.

    Article  PubMed  CAS  Google Scholar 

  • Stackman, R. W., Eckenstein, F., Frei, B., Kulhanek, D., Nowlin, J., & Quinn, J. F. (2003). Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment. Experimental Neurology, 184, 510–520.

    Article  PubMed  Google Scholar 

  • Suh, J. H., Wang, H., Liu, R. M., Liu, J., & Hagen, T. M. (2004). (R)-alpha-lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: Evidence for increased cysteine requirement for GSH synthesis. Archives of Biochemistry and Biophysics, 423, 126–135.

    Article  PubMed  CAS  Google Scholar 

  • Thal, L. J., Grundman, M., Berg, J., Ernstrom, K., Margolin, R., Pfeiffer, E., et al. (2003). Idebenone treatment fails to slow cognitive decline in Alzheimer's disease. Neurology, 61, 1498–1502.

    PubMed  CAS  Google Scholar 

  • Wallace, D. C. (1999). Mitochondrial diseases in man and mouse. Science, 283, 1482–1488.

    Article  PubMed  CAS  Google Scholar 

  • Wang, J., Xiong, S., Xie, C., Markesbery, W. R., & Lovell, M. A. (2005). Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease. Journal of Neurochemistry, 93, 953–962.

    Article  PubMed  CAS  Google Scholar 

  • Weyer, G., Babej-Dolle, R. M., Hadler, D., Hofmann, S., & Herrmann, W. M. (1997). A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease. Neuropsychobiology, 36, 73–82.

    Article  PubMed  CAS  Google Scholar 

  • Yamada, K., Tanaka, T., Han, D., Senzaki, K., Kameyama, T., & Nabeshima, T. (1999). Protective effects of idebenone and alpha-tocopherol on beta-amyloid-(1–42)-induced learning and memory deficits in rats: Implication of oxidative stress in beta-amyloid-induced neurotoxicity in vivo. The European Journal of Neuroscience, 11, 83–90.

    Article  PubMed  CAS  Google Scholar 

  • Yao, Z. X., Han, Z., Drieu, K., & Papadopoulos, V. (2004). Ginkgo biloba extract (Egb 761) inhibits beta-amyloid production by lowering free cholesterol levels. The Journal of Nutritional Biochemistry, 15, 749–756.

    Article  PubMed  CAS  Google Scholar 

  • Zandi, P. P., Anthony, J. C., Khachaturian, A. S., Stone, S. V., Gustafson, D., Tschanz, J. T., et al. (2004). Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: The Cache County Study. Archives of Neurology, 61, 82–88.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Case Western Reserve University, Cleveland, OH, USA

    Paula I. Moreira, Mark A. Smith, Xiongwei Zhu & George Perry

  2. Department of Psychiatry and Neurology, Asahikawa Medical College, Asahikawa, Japan

    Akihiko Nunomura

Authors
  1. Paula I. Moreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark A. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiongwei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akihiko Nunomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. George Perry
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Moreira, P.I., Smith, M.A., Zhu, X., Nunomura, A., Perry, G. (2007). The Potential Application of Antioxidant Agents in Alzheimer Disease Therapeutics. In: Pharmacological Mechanisms in Alzheimer's Therapeutics. Springer, New York, NY. https://doi.org/10.1007/978-0-387-71522-3_12

Download citation

Publish with us

Policies and ethics

Search

Navigation