Skip to main content
SpringerLink
Log in

Oxidative stress in Alzheimer’s Disease: Implications for Prevention and Therapy

  • Chapter
Alzheimer’s Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 38))

Abstract

Oxidative stress is a marker of neurodegeneration and has been recently shown to be also involved in the early stages of the pathogenesis of various neurodegenerative disorders. In general, all biomolecules of the cell can be oxidized and thereby damaged. Consequently, the concept of neuroprotection by antioxidants has been developed. In many cases the direct scavanging of free radicals have been used as a strategy to prevent oxidative stress damage and a variety of physiological and synthetic antioxidant molecules have been identified and synthesized including the female sex homone estrogen. In Alzheimer’s Disease amyloid-β protein on its way to brain deposition can also induce oxidative changes rendering nerve cells more vulnerable to additional insults. In addition, inflammatory mediators are attracted by amyloid deposits that can further speed up the generation of an oxidative micro-environment. Based on recent clinical data the use of a combination of various antioxidants might indeed be effective in preventing Alzheimer’s Disease. Nevertheless, the exact molecular mechanisms and the real impact of oxidative stress on the development and progression of Alzheimer’s Disease as well as of other neurodegenerative disorders still needs to be further investigated.

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  • Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G.M., Cooper, N.R., Eikelenboom, P., Emmerling, M., Fiebich, B.L., Finch, C.E., Frautschy, S., Griffin, W.S., Hampel, H., Hull, M., Landreth, G., Lue, L., Mrak, R., Mackenzie, I.R., McGeer, P.L., O’Banion, M.K., Pachter, J., Pasinetti, G., Plata-Salaman, C., Rogers, J., Rydel, R., Shen, Y., Streit, W., Strohmeyer, R., Tooyoma, I., Van Muiswinkel, F.L., Veerhuis, R., Walker, D., Webster, S., Wegrzyniak, B., Wenk, G., and Wyss-Coray, T., 2000, Inflammation and Alzheimer’s disease. Neurobiol. Aging. 21: 383–421.

    Article  PubMed  CAS  Google Scholar 

  • Ames, B.N, Shigenda, M.K, and Hagen, T.M., 1993, Oxidants, antioxidants, and the degenerative diseases of aging. Proc Nad Acad Sci USA 90: 7915–7922.

    Article  CAS  Google Scholar 

  • Babior, B.M., 2000, Phagocytes and oxidative stress. Am. J. Med. 109: 33–44.

    Article  PubMed  CAS  Google Scholar 

  • Behl, C., 2002, Oestrogen as a neuroprotective hormone. Nat. Rev. Neuro Sci. 3: 433–442.

    CAS  Google Scholar 

  • Behl, C., Davis, J., Cole, G.M., and Schubert, D., 1992, Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem. Biophys. Res. Commun. 186: 944–950.

    Article  PubMed  CAS  Google Scholar 

  • Behl, C., Davis, J.B., Lesley R., and Schubert, D.,. 1994, Hydrogen peroxide mediates amyloid beta protein atomicity. Cell 77: 817–827.

    Article  PubMed  CAS  Google Scholar 

  • Breitner, J.C., and Zandi, P.P., 2001, Do nonsteroidal antiinflammatory drugs reduce the risk of Alzheimer’s disease? N. Engl. J. Med. 345: 1567–1568.

    Article  PubMed  CAS  Google Scholar 

  • Brusco, L.I., Marquez, M., and Cardinali, D.P., 2000, Melatonin treatment stabilizes chronobiologic and cognitive symptoms in Alzheimer’s disease. Neuroendocrinol. Lett. 21: 39–42.

    PubMed  Google Scholar 

  • Carlson, M.C., Zandi, P.P., Plassman, B.L., Tschanz, J.T., Welsh-Bohmer, K.A., Steffens, D.C., Bastian, L.A., Mehta, K.M., and Breitner, J.C., 2001, Cache County Study Group. Hormone replacement therapy and reduced cognitive decline in older women: the Cache County Study. Neurology 57: 2210–2216.

    PubMed  CAS  Google Scholar 

  • Christen, Y., 2000, Oxidative stress and Alzheimer disease. Am. J. Clin. Nutr. 71: 621S–629S.

    PubMed  CAS  Google Scholar 

  • Crapper McLachlan, D.R., Dalton, A.J., Kruck, T.P., Bell, M.Y., Smith, W.L., Kalow, W., Andrews, D.F., 1991, Intramuscular desferrioxamine in patients with Alzheimer’s disease. Lancet 337: 1304–1308.

    Article  PubMed  CAS  Google Scholar 

  • Dewachter, I., van Dorpe, J., Spittaels, K., Tesseur, I., Van Den Haute, C., Moechars, D., Van Leuven, F., 2000, Modeling Alzheimer’s disease in transgenic mice: effect of age and of presenilinl on amyloid biochemistry and pathology in APP/London mice. Exp. Gerontol. 35: 831–841.

    Article  PubMed  CAS  Google Scholar 

  • Floyd, R.A., 1999, Antioxidants, oxidative stress, and degenerative neurological disorders. Proc. Soc. Exper. Biol. Med. 222: 236–245.

    Article  CAS  Google Scholar 

  • Galeazzi, L., Ronchi, P., Franceschi, C., and Giunta, S., 1999, In vitro peroxidase oxidation induces stable dimers of beta-amyloid (1-42) through dityrosine bridge formation. Amyloid 6: 7–13.

    PubMed  CAS  Google Scholar 

  • Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F, et al., 1995, Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature 373: 523–527.

    Article  PubMed  CAS  Google Scholar 

  • Gouras, G.K., and Beal, M.F., 2001, Metal chelator decreases Alzheimer beta-amyloid plaques. Neuron 30: 641–642.

    Article  PubMed  CAS  Google Scholar 

  • Grundman, M.. 2000, Vitamin E and Alzheimer disease: the basis for additional clinical trials. Am. J. Clin. Nutr. 71: 630S–636S.

    PubMed  CAS  Google Scholar 

  • Gutzmann, H., and 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. J. Neural. Transm. Suppl. 54: 301–310.

    CAS  Google Scholar 

  • Halliwell, B., and Gutteridge, J.M.C., 2003, Free Radicals in Biology and Medicine. Oxford University Press.

    Google Scholar 

  • Harman D., 1992, Free radical theory of aging. Mutan Res. 275: 257–266.

    CAS  Google Scholar 

  • Harman D., 1996, A hypothesis on pathogenesis of Alzheimer’s disease. Ann. NY Acad. Sci. 786: 152–168.

    PubMed  CAS  Google Scholar 

  • Holcomb, L., Gordon, M.N., McGowan, E., Yu, X., Benkovic, S., Jantzen, P., Wright, K., Saad, I., Mueller, R., Morgan, D., Sanders, S., Zehr, C., O’Campo, K., Hardy, J., Prada, C.M., Eckman, C., Younkin, S., Hsiao, K., and Duff, K., 1998, Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nature Med. 1: 97–100.

    Google Scholar 

  • Huang, X., Cuajungco, M.P., Atwood, C.S., Hartshorn, M.A., Tyndall, J.D., Hanson, G.R., Stokes, K.C., Leopold, M., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Saunders, A.J., Lim, J., Moir, R.D., Glabe, C., Bowden, E.F., Masters, C.L., Fairlie, D.P., Tanzi, R.E., and Bush, A.I., 1999, Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J. Biol. Chem. 274: 37111–37116.

    Article  PubMed  CAS  Google Scholar 

  • in t’ Veld, B..A., Ruitenberg, A., Hofman, A., Launer, L.J., van Duijn, C.M., Stijnen, T., Breteler, M.M., and Stricker, B.H. 2001, Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N. Engl. J. Med. 345: 1515–1521.

    Article  Google Scholar 

  • Joseph, J, Skuitt-Hale, B, Denisova, N.A, Martin, A, Perry, G, and Smith, M.A, 2001, Copernicus revisited: amyloid β in Alzheimer’s disease. Neurobiol.. Aging 22: 131–146.

    Article  PubMed  CAS  Google Scholar 

  • Klotz, L.O., Sies, H., 2003, Defenses against peroxynitrite: selenocompounds and flavonoids. Toxicol Lett. 140–141: 125–132.

    Article  PubMed  CAS  Google Scholar 

  • Koppaka, V., and Axelsen, P.H., 2000, Accelerated accumulation of amyloid beta proteins on oxidatively damaged lipid membranes. Biochemistry 39: 10011–10016.

    Article  PubMed  CAS  Google Scholar 

  • Markesberry, W.R., and Carney, J.M., 1999, Oxidative alterations in Alzheimer’s disease. Brain Pathol. 9: 133–146.

    Article  Google Scholar 

  • McGeer, P.L., and, McGeer, E.G., 1996, Anti-inflammatory drugs in the fight against Alzheimer’s disease. Ann. N. Y. Acad. Sci. 777: 213–220.

    PubMed  CAS  Google Scholar 

  • McGeer, P.L., and Rogers, J., 1992, Anti-inflammatory agents as a therapeutic approach to Alzheimer’s disease. Neurology 42: 447–449.

    PubMed  CAS  Google Scholar 

  • Moosmann, B., and Behl, C., 1999, The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proc. Natl. Acad. Sci. USA 96: 8867–8872.

    Article  PubMed  CAS  Google Scholar 

  • Moosmann, B., and Behl, C., 2002, Antioxidants as treatment for neurodegenerative disorders. Expert Opin. Investig. Drugs. 11: 1407–1435.

    Article  PubMed  CAS  Google Scholar 

  • Nunomura, A., Perry, G., Pappolla, M.A., Friedland, R.P., Hirai, K., Chiba, S., and Smith M.A., 2000, Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. J. Neuropathol. Ex.p Neurol. 59: 1011–1017.

    CAS  Google Scholar 

  • Nunomura, A., Perry, G., Aliev, G., et al., 2001, Cytosolic peroxidative damage is an early event in Alzheimer’s disease. J. Neuropathol. Exp. Neurol. 60: 759–767.

    PubMed  CAS  Google Scholar 

  • Nourhashemi, F., Gillette-Guyonnet, S., Andrieu, S., Ghisolfi, A., Ousset, P.J., Grandjean, H., Grand, A., Pous, J., Vellas, B., and Albarede, J.L., 2000, Alzheimer disease: protective factors. Am. J. Clin. Nutr. 71: 643S–649S.

    PubMed  CAS  Google Scholar 

  • Oken, B.S., Storzbach, D.M., and Kaye, J.A., 1998, The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease. Arch. Neurol. 55: 1409–1415.

    Article  PubMed  CAS  Google Scholar 

  • Paganini-Hill, A., and Henderson, V.W., 1996, Estrogen replacement therapy and risk of Alzheimer disease. Arch Intern Med. 156: 2213–2217.

    Article  PubMed  CAS  Google Scholar 

  • Perutz, M.F., and Windle, A.H., 2001, Cause of neural death in neurodegenerative diseases attributable to expansion of glutamine repeats. Nature 412: 143–144.

    Article  PubMed  CAS  Google Scholar 

  • Pratico, D., and Delanty, N., 2000, Oxidative injury in diseases of the central nervous system: focus on Alzheimer’s disease. Am. J. Med. 109: 577–585.

    Article  PubMed  CAS  Google Scholar 

  • Pratico, D, Uryu, K, Leight, S., Trojanoswki, J.Q., and Lee, V.M., 2001, Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J. Neuro Sci. 21: 4183–4187.

    CAS  Google Scholar 

  • Sano, M., Ernesto, C., Thomas, R.G., Klauber, M.R., Schafer, K., Grundman, M., Woodbury, P., Growdon, X, Cotman, C.W., Pfeiffer, E., Schneider, L.S., and Thal, L.J., 1997, A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. N. Engl. J. Med. 336: 1216–1222.

    Article  PubMed  CAS  Google Scholar 

  • Selkoe, D.J., 1999, Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature 399 (Supp I) A23–31.

    Article  PubMed  CAS  Google Scholar 

  • Sies, H., 1993, Strategies of antioxidant defense. Eur. J. Bio Chem. 215: 213–219.

    CAS  Google Scholar 

  • Smith, M.A., Harris, P.L., Sayre, L.M., and Perry, G., 1997, Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc. Nat.l Acad. Sci. USA. 1997 94: 9866–9868.

    Article  CAS  Google Scholar 

  • Spagnoli, A., Lucca, U., Menasce, G., Bandera, L., Cizza, G., Forloni, G., Tettamanti, M., Frattura, L., Tiraboschi, P., Comelli, M., et al., 1991, Long-term acetyl-L-carnitine treatment in Alzheimer’s disease. Neurology 41: 1726–1732.

    PubMed  CAS  Google Scholar 

  • Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.H., Mistl, C., Rothacher, S., Ledermann, B., Burki, K., Frey, P., Paganetti, P.A., Waridel, C., Calhoun, M.E., Jucker, M., Probst, A., Staufenbiel, M., and Sommer, B., 1997, Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl. Acad. Sci. USA 94: 13287–13292.

    Article  PubMed  CAS  Google Scholar 

  • Tang, M.X., Jacobs, D., Stern, Y., Marder, K., Schofield, P., Gurland, B., Andrews, H., and Mayeux, R., 1996, Effect of oestrogen during menopause on risk and age at onset of Alzheimer’s disease. Lancet 348: 429–432.

    Article  PubMed  CAS  Google Scholar 

  • Thal, L.J., Calvani, M., Amato, A., and Carta, A., 2000, A 1-year controlled trial of acetyl-1-carnitine in early-onset AD. Neurology 55: 805–810.

    PubMed  CAS  Google Scholar 

  • Thal, L.J., Carta, A., Clarke, W.R., Ferris, S.H., Friedland, R.P., Petersen, R.C., Pettegrew, J.W., Pfeiffer, E., Raskind, M.A., Sano, M., Tuszynski, M.H., and Woolson, R.F., 1996, A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer’s disease. Neurology 47: 705–711.

    PubMed  CAS  Google Scholar 

  • Walsh, D.M., Klyubin, I., Fadeeva, J.V., Cullen, W.K., Anwyl, R., Wolfe, M.S., Rowan, M.J., and Selkoe, D.J., 2002, Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535–539.

    Article  PubMed  CAS  Google Scholar 

  • Waring, S.C., Rocca, W.A., Petersen, R.C., O’Brien, P.C., Tangalos, E.G., and Kokmen, E., 1999, Postmenopausal estrogen replacement therapy and risk of AD: a population-based study. Neurology 52: 965–970.

    PubMed  CAS  Google Scholar 

  • Weggen, S., Eriksen, J.L., Das, P., Sagi, S.A., Wang, R., Pietrzik, C.U., Findlay, K.A., Smith, T.E., Murphy, M.P., Bulter, T., Kang, D.E., Marquez-Sterling, N., Golde, T.E., and Koo, E.H., 2001, A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414: 212–216.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Zandi, P.P., Anthony, J.C., Khachaturian, A.S., Stone, S.V., Gustafson, D., Tschanz, J.T., Norton, M.C., Welsh-Bohmer, K.A., and Breitner, J.C., 2004, Cache County Study Group. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study. Arch. Neurol. 61: 82–88.

    Article  PubMed  Google Scholar 

  • Zandi, P.P., and Breitner, J.C., 2001, Do NSAIDs prevent Alzheimer’s disease? And, if so, why? The epidemiological evidence. Neurobiol Aging 22: 811–817.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Physiological Chemistry & Pathobiochemistry, Faculty of Medicine, Johannes Gutenberg University, Mainz, Duesbergweg 6, D-55099, Mainz, Germany

    Christian Behl

Authors
  1. Christian Behl
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Zoology, University of Mainz, Mainz, Germany

    J. Robin Harris

  2. Institute of Biochemistry, University of Mainz, Mainz, Germany

    Falk Fahrenholz

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer Science+Business Media, Inc.

About this chapter

Cite this chapter

Behl, C. (2005). Oxidative stress in Alzheimer’s Disease: Implications for Prevention and Therapy. In: Harris, J.R., Fahrenholz, F. (eds) Alzheimer’s Disease. Subcellular Biochemistry, vol 38. Springer, Boston, MA . https://doi.org/10.1007/0-387-23226-5_3

Download citation

Publish with us

Policies and ethics

Search

Navigation