Association between enzymatic and non-enzymatic antioxidant defense mechanism with apolipoprotein E genotypes in Alzheimer disease.
OBJECTIVE
There are evidence suggesting that APOE-varepsilon4 allele play an important role in the pathogenesis of Alzheimer's disease (AD) by reducing peripheral levels and activities of a broad spectrum of nonenzymatic and enzymatic antioxidants systems. However, the link between APOE genotype, oxidative stress, and AD has yet to be established. In this study we examined whether antioxidant defense mechanism exacerbates the risk of AD in individual carrying APOE-varepsilon4 allele in a population from Tehran, Iran.


METHODS
We determined the enzymatic activities of the erythrocyte Cu-Zn superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and serum level of total antioxidant status(TAS) in various APOE genotypes in 91 patients with AD and 91 healthy subjects as control group (age and sex-matched).


RESULTS
The results showed that the TAS level and the activities of enzymatic antioxidants CAT and GSH-Px were significantly lower and the SOD activity was significantly higher in AD patients compared to controls. The AD patients with APOE-varepsilon4 allele genotype had significantly lower serum TAS concentration and lower erythrocytes GSH-Px and CAT activities (p=0.001) but significantly higher erythrocytes Cu-Zn SOD activity (p=0.001) than the non-APOE-varepsilon4 carrier AD and the control group. In addition, the association observed between the factors involved in an antioxidant defense mechanism and APOE-varepsilon4 allele in AD increased with age of the subjects.


CONCLUSIONS
These data indicate that the reduced serum level of TAS and activity of CAT, GSH-Px and increased SOD exacerbate the risk of AD in individuals carrying APOE-varepsilon4 allele. The reduced antioxidants defense in APOE-varepsilon4 allele carrier may contribute to beta-amyloidosis. This effect, however, is more pronounced in the AD patients older than 75 years of age. This suggests that a therapeutic modality should be considered for these subjects.
Kharrazi
Hadi
H
Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Danshgah Avenue, Postal code: 67148-69914, Kermanshah, Iran.
Vaisi-Raygani
Asad
A
Rahimi
Zohreh
Z
Tavilani
Haidar
H
Aminian
Mahdi
M
Pourmotabbed
Tayebeh
T
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D000975:Antioxidants / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D002374:Catalase / Q000097:blood; D004247:DNA / Q000235:genetics; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000097:blood
D000975:Antioxidants; D053327:Apolipoprotein E4; D004247:DNA; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase