Unaltered brain levels of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal in Alzheimer's disease.
In recent years, an important role for the pathogenesis of Alzheimer's disease (AD) has been ascribed to oxidative stress. Trans-4-hydroxy-2-nonenal, a product of lipid peroxidation, forms stable adducts with a variety of nucleophilic substituents such as thiols or amino moieties. Here, we report the quantification of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal (HNE-dGp) using the specific and very sensitive method of 32P-postlabeling of deoxyguanosine adducts derived from nuclear DNA in neuron rich areas of the hippocampus, the parietal cortex, and the cerebellum of postmortem brains from patients with AD and age matched controls. Adduct levels were highest in the hippocampus, followed by the cerebellum and parietal cortex irrespective of the disease. Neither age, postmortem delay time, gender, nor the extent of neurofibrillary deposits affected tissue adduct levels in the brain areas examined. Although distinctively present in the human brain, the level of HNE-dGp adducts appears not to be useful as a biomarker for AD.
Götz
M E
ME
Department of Toxicology, University of Würzburg, Germany. ennio@mail.uni-wuerzburg.de
Wacker
M
M
Luckhaus
C
C
Wanek
P
P
Tatschner
T
T
Jellinger
K
K
Leblhuber
F
F
Ransmayr
G
G
Riederer
P
P
Eder
E
E
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology*; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors
D000447:Aldehydes; D015415:Biomarkers; C060934:1,N(2)-propanodeoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal