Unaltered brain levels of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal in Alzheimer's disease.

Full Abstract

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.

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Author information

Author/s: Götz, M E (ME); 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);

Affiliation: Department of Toxicology, University of Würzburg, Germany. ennio(-atsign-)mail.uni-wuerzburg.de

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neuroscience letters (Neurosci Lett), published in Ireland. (Language: eng)

Reference: 2002-May; vol 324 (issue 1) : pp 49-52

Dates: Created 2002/05/01; Completed 2002/07/12; Revised 2006/11/15;

PMID: 11983292, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Age Factors
Aged
Aged, 80 and over
Aldehydes - metabolism
Alzheimer Disease - metabolism; pathology; physiopathology
Biological Markers
Brain - metabolism; pathology; physiopathology
Brain Chemistry - physiology
Cerebellum - metabolism; pathology; physiopathology
Deoxyguanosine - analogs & derivatives; metabolism
Female

Female
Hippocampus - metabolism; pathology; physiopathology
Humans
Lipid Peroxidation - physiology
Male
Neurofibrillary Tangles - metabolism; pathology
Neurons - metabolism; pathology
Oxidative Stress - physiology
Parietal Lobe - metabolism; pathology; physiopathology
Senile Plaques - metabolism; pathology
Sex Factors

Associated Chemicals: Aldehydes (0) ; Biological Markers (0) ; 1,N(2)-propanodeoxyguanosine (120667-07-4) ; 4-hydroxy-2-nonenal (29343-52-0) ; Deoxyguanosine (961-07-9)

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