Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease.

Abstract

A large body of experimental evidence suggests that in Alzheimer disease (AD) pathogenesis an important role is played by oxidative stress, but there is still a lack of data on in vivo markers of free radical-induced damage. To evaluate levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage to DNA, in peripheral lymphocytes; to measure plasma concentrations of several nonenzymatic antioxidants; and to assess the relationships between any observed changes in lymphocyte DNA 8-OHdG content and plasma antioxidant levels in patients with AD and healthy aged control subjects. Forty elderly outpatients with AD and 39 healthy age- and sex-matched controls were studied. The level of 8-OHdG was determined in DNA extracted from lymphocytes and plasma levels of vitamin C, vitamin A, vitamin E, and carotenoids (zeaxanthin, beta-cryptoxanthin, lycopene, lutein, and alpha- and beta-carotene) were measured by high-performance liquid chromatography. Lymphocyte DNA 8-OHdG content was significantly higher and plasma levels of antioxidants (with the exception of lutein) were significantly lower in patients with AD compared with controls. In patients with AD, a significant inverse relationship between lymphocyte DNA 8-OHdG content and plasma levels of lycopene, lutein, alpha-carotene, and beta-carotene, respectively, was observed. Markers of oxidative damage are increased in AD and correlate with decreased levels of plasma antioxidants. These findings suggest that lymphocyte DNA 8-OHdG content in patients with AD reflects a condition of increased oxidative stress related to a poor antioxidant status.