Oxidative damage in the olfactory system in Alzheimer's disease.
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.
Perry
George
G
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA. gxp7@po.cwru.edu
Castellani
Rudy J
RJ
Smith
Mark A
MA
Harris
Peggy L R
PL
Kubat
Zvezdana
Z
Ghanbari
Kasra
K
Jones
Paul K
PK
Cordone
Giovanni
G
Tabaton
Massimo
M
Wolozin
Benjamin
B
Ghanbari
Hossein
H
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008565:Membrane Proteins; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D009831:Olfactory Mucosa / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1