Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
Forty elderly outpatients with AD and 39 healthy age- and sex-matched controls were studied.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mecocci
Patrizia
P
Institute of Gerontology and Geriatrics, University of Perugia, Via Eugubina 42, 06122 Perugia, Italy. mecocci@unipg.it
Polidori
M Cristina
MC
Cherubini
Antonio
A
Ingegni
Tiziana
T
Mattioli
Paola
P
Catani
Marco
M
Rinaldi
Patrizia
P
Cecchetti
Roberta
R
Stahl
Wilhelm
W
Senin
Umberto
U
Beal
M Flint
MF
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D016014:Linear Models; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D000975:Antioxidants; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine