Acta Neuropathologica

, Volume 106, Issue 6, pp 552–556 | Cite as

Oxidative damage in the olfactory system in Alzheimer's disease

  • George Perry
  • Rudy J. Castellani
  • Mark A. Smith
  • Peggy L. R. Harris
  • Zvezdana Kubat
  • Kasra Ghanbari
  • Paul K. Jones
  • Giovanni Cordone
  • Massimo Tabaton
  • Benjamin Wolozin
  • Hossein Ghanbari
Regular Paper

Abstract

Increased oxidative damage is a prominent and early feature of vulnerable neurons in Alzheimer's disease (AD). However, while damage to proteins, sugars, lipids, nucleic acids and organelles such as lysosomes, mitochondria, and endoplasmic reticulum are evident, the source of increased reactive oxygen species has not been determined. Furthermore, a major limitation in further determining the source, as well as finding a means to arrest damage, is the paucity of cellular models directly homologous to AD since the vulnerable neurons of the brain in AD cannot be studied in vitro. Here, we examined the olfactory epithelium in situ to see if neurons there exhibit a similar pathological oxidative balance to vulnerable neurons in AD. In biopsy specimens, (eight AD and three controls) we found that neurons, and also the surrounding epithelial cells, show an increase in oxidative damage for a subset of the markers increased in the brain of cases of AD. Lipid peroxidation and heme oxygenase-1, a stress response protein, were increased, while nucleic acid or protein oxidation, demonstrated in vulnerable neurons in AD, were not increased. These findings highlight the systemic nature of oxidative abnormalities in AD, but that different cell types may express this abnormality by a different array of oxidative stress markers, supporting the potential for using olfactory neurons or other cells derived from AD patients in culture to understand the mechanistic basis for increased oxidative damage in AD and as a model to screen compounds for therapeutic intervention.

Keywords

Alzheimer's disease Heme oxygenase Lipid peroxidation Olfactory neurons Oxidative stress 

Notes

Acknowledgements

This work was supported by the National Institutes of Health, the Alzheimer's Association, and Panacea Pharmaceuticals. Mark A. Smith and George Perry are compensated consultants and own equity in Panacea Pharmaceuticals.

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • George Perry
    • 1
  • Rudy J. Castellani
    • 1
  • Mark A. Smith
    • 1
  • Peggy L. R. Harris
    • 1
  • Zvezdana Kubat
    • 1
  • Kasra Ghanbari
    • 2
  • Paul K. Jones
    • 3
  • Giovanni Cordone
    • 4
  • Massimo Tabaton
    • 5
  • Benjamin Wolozin
    • 6
  • Hossein Ghanbari
    • 2
  1. 1.Institute of PathologyCase Western Reserve UniversityClevelandUSA
  2. 2.Panacea PharmaceuticalsRockvilleUSA
  3. 3.Epidemiology and BiostatisticsCase Western Reserve UniversityClevelandUSA
  4. 4.Department of OtorhinolaryngologyUniversity of GenoaGenoaItaly
  5. 5.Department of NeurologyUniversity of GenoaGenoaItaly
  6. 6.Department of PharmacologyLoyola University Medical CenterMaywoodUSA

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