8OHdG levels in brain do not indicate oxidative DNA damage in Alzheimer's disease.
Accumulation of oxidative DNA damage has been proposed to underlie aging and neurodegenerative diseases such as Alzheimer's Disease (AD). The DNA adduct 8-hydroxy-2'-deoxyguanosine (8OHdG) is considered a good indicator of oxidative DNA damage. To investigate whether this type of DNA damage is involved in AD etiology, 8OHdG levels were determined in postmortem human brain tissue of controls and AD patients (in frontal, occipital, and temporal cortex and in hippocampal tissue). Parametric studies in rat revealed no influences of postmortem delay, repeated freezing/thawing or storage time. In human brain, approximately two 8OHdG molecules were present per 10(5) 2'-deoxyguanosines. In AD patients and controls, 8OHdG-levels were not related to age, sex, or brain region. Also, no differences were found between controls and AD patients. It was concluded that 8OHdG in nuclear DNA, although present throughout the brain in fairly high amounts, does not accumulate with age, nor does it appear to be involved in AD. More detailed studies are required to extend this conclusion to other types of oxidative damage.
Te Koppele
J M
JM
TNO Prevention and Health, Division of Vascular and Connective Tissue Research, Gaubius Laboratory, Leiden, The Netherlands.
Lucassen
P J
PJ
Sakkee
A N
AN
Van Asten
J G
JG
Ravid
R
R
Swaab
D F
DF
Van Bezooijen
C F
CF
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology*; D002540:Cerebral Cortex / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis; D004249:DNA Damage / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004563:Electrochemistry; D005260:Female; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D011180:Postmortem Changes; D013048:Specimen Handling
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine