Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients

Hossein A. Ghanbari, Kasra Ghanbari, Peggy L.R. Harris, Paul K. Jones, Zvezdana Kubat, Rudolph J. Castellani, Benjamin L. Wolozin, Mark A. Smith, George Perry*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

80 Scopus citations

Abstract

Oxidative abnormalities precede clinical and pathological manifestations of Alzheimer's disease and are the earliest pathological changes reported in the disease. The olfactory pathways and mucosa also display the pathological features associated with Alzheimer's disease in the brain. Olfactory neurons are unique because they can undergo neurogenesis and are able to be readily maintained in cell culture. In this study, we examined neuronal cell cultures derived from olfactory mucosa of Alzheimer's disease and control patients for oxidative stress responses. Levels of lipid peroxidation (hydroxynonenal), NE-(carboxymethyl) lysine (glycoxidative and lipid peroxidation), and oxidative stress response (heme oxygenase-1) were measured immunocytochemically. We found increased levels for all the oxidative stress markers examined in Alzheimer's disease neurons as compared to controls. Interestingly, in one case of Alzheimer's disease, we found hydroxynonenal adducts accumulated in cytoplasmic lysosome-like structures in about 20% of neurons cultured, but not in neurons from control patients. These lysosome-like structures are found in about 100% of the vulnerable neurons in brains of cases of Alzheimer's disease. This study suggests that manifestations of oxidative imbalance in Alzheimer's disease extend to cultured olfactory neurons. Primary culture of human olfactory neurons will be useful in understanding the mechanism of oxidative damage in Alzheimer's disease and can even be utilized in developing therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)41-44
Number of pages4
JournalAging Cell
Volume3
Issue number1
DOIs
StatePublished - Feb 2004

Keywords

  • 4-hydroxynonenal
  • Alzheimer's disease
  • Cell culture
  • Lipid peroxidation
  • Olfactory neurons
  • Oxidative stress

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Fingerprint

Dive into the research topics of 'Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients'. Together they form a unique fingerprint.

Cite this