Peripheral antioxidant enzyme activities and selenium in elderly subjects and in dementia of Alzheimer's type--place of the extracellular glutathione peroxidase.
Defenses against free radical damage were determined in red blood cells and plasma from 40 patients with dementia of the Alzheimer-type (DAT) and 34 aged control subjects with normal cognitive function. No crude significant difference in erythrocyte copper-zinc superoxide dismutase (E-CuZnSOD), seleno-dependent glutathione peroxidase (E-GSH-Px), glutathione reductase (E-GSSG-RD) activities, and selenium (Se) concentration was found between DAT cases and control subjects. The peroxidation products evaluated in plasma by the thiobarbituric-reactive material (TBARS) were at the same level in the DAT group as compared to controls. In the DAT group, plasma GSH-Px (P-GSH-Px) activity and plasma Se (P-Se) were negatively correlated with age (r = -0.58; p < 0.001 and r = -0.63; p < 0.001 respectively). Moreover, erythrocyte GSH-Px activity and Se were also negatively correlated with age (r = -0.40; p < 0.01 and r = -0.46; p < 0.01, respectively). No significant correlation with age was observed in the controls. When controlling for age, a significant increase for P-GSH-Px activity and P-Se was observed in DAT patients as compared to controls. These significant differences mostly appeared in DAT subjects under 80 years. Some correlations were only observed in the DAT group such as P-GSH-Px and E-GSH-Px (r = +0.68; p < 0.001); P-GSH-Px and E-Se (r = +0.79; p < 0.001). Correlations between P-GSH-Px and P-Se, E-GSH-Px and P-Se, and P-Se with E-Se are greater in the DAT group (r = +0.84; p < 0.001; r = +0.76; p < 0.001 and r = 0.75; p < 0.001) than in the control group (r = 0.54, pI < 0.01; r = 0.43, p < 0.01 and r = +0.34, p < 0.05 respectively). The fact that first -- a significant increase in P-GSH-Px and P-Se, second -- some modifications in the relationships between antioxidant parameters, and third -- age-dependent decreases of glutathione-peroxidase activities and their cofactor, appeared only in the DAT group suggest that DAT is associated with an oxidative stress due to an imbalance between reactive oxygen species and the peripheral antioxidant opposing forces.
Ceballos-Picot
I
I
Department of Biochemistry B and A, Necker Hospital, Paris, France.
Merad-Boudia
M
M
Nicole
A
A
Thevenin
M
M
Hellier
G
G
Legrain
S
S
Berr
C
C
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000201:enzymology*; D000975:Antioxidants / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D006801:Humans; D008297:Male; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase