This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (40)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Alzheimer Disease  • Neuropathology  • Alert me on articles by topic

Mark A. Lovell, PhD; William R. Markesbery, MD

Arch Neurol. 2001;58:392-396.

Background  Markers of oxidative stress are increased in cerebrospinal fluid (CSF) of patients with Alzheimer disease (AD), although none of those reported are appropriate diagnostic markers because of the overlap between patients with AD and control subjects.

Objective  To determine the ratio of 8-hydroxyguanine (8-OHG) levels in intact DNA to free 8-OHG in the ventricular CSF of patients with AD and age-matched control subjects. The most prominent marker of DNA oxidation is 8-OHG.

Methods  Free 8-hydroxy-2'-deoxyguanosine (8-OHdG) was isolated from ventricular CSF taken at autopsy from 18 subjects with AD and 7 control subjects using solid-phase extraction columns. Levels were measured as the hydrolysis product, 8-OHG, using gas chromatography/mass spectrometry with selective ion monitoring. Intact DNA was isolated from the same CSF and the levels of 8-OHG were determined in the intact structures. Stable-labeled 8-OHG was used for quantification.

Results  A statistically significant (P<.05) 108-fold increase in the ratio of 8-OHG in intact DNA to free 8-OHG was observed in patients with AD. Analysis of the data distribution indicated that the lowest AD ratio was 3.5 times higher than the highest control ratio; there was no overlap of the 2 populations.

Conclusion  Although the data for each individual measurement demonstrates overlap between patients with AD and control subjects, the ratio of 8-OHG intact in DNA to free 8-OHG demonstrates a delineation between patients with AD and control 8-OHG subjects and may be useful as a marker of disease progression or the efficacy of therapeutic antioxidant intervention.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Identification and characterization of OGG1 mutations in patients with Alzheimer's disease
Mao et al.
Nucleic Acids Res 2007;0:gkm189v1-8.
ABSTRACT | FULL TEXT  

The Chk1/Cdc25A Pathway as Activators of the Cell Cycle in Neuronal Death Induced by Camptothecin.
Zhang et al.
J. Neurosci. 2006;26:8819-8828.
ABSTRACT | FULL TEXT  

Differential Roles of Nuclear and Cytoplasmic Cyclin-Dependent Kinase 5 in Apoptotic and Excitotoxic Neuronal Death
O'Hare et al.
J. Neurosci. 2005;25:8954-8966.
ABSTRACT | FULL TEXT  

Ribosomal RNA in Alzheimer Disease Is Oxidized by Bound Redox-active Iron
Honda et al.
J. Biol. Chem. 2005;280:20978-20986.
ABSTRACT | FULL TEXT  

Nuclear Factor-{kappa}B Modulates the p53 Response in Neurons Exposed to DNA Damage
Aleyasin et al.
J. Neurosci. 2004;24:2963-2973.
ABSTRACT | FULL TEXT  

High Concentrations of Excised Oxidative DNA Lesions in Human Cerebrospinal Fluid
Rozalski et al.
Clin. Chem. 2003;49:1218-1221.
FULL TEXT  

The Identification and Characterization of Oxidized RNAs in Alzheimer's Disease
Shan et al.
J. Neurosci. 2003;23:4913-4921.
ABSTRACT | FULL TEXT  

Alzheimer Disease: Current Concepts and Emerging Diagnostic and Therapeutic Strategies
Clark and Karlawish
ANN INTERN MED 2003;138:400-410.
ABSTRACT | FULL TEXT  

Lymphocyte Oxidative DNA Damage and Plasma Antioxidants in Alzheimer Disease
Mecocci et al.
Arch Neurol 2002;59:794-798.
ABSTRACT | FULL TEXT  

Dementia: New Data and Practice Guidelines
JWatch Psychiatry 2001;2001:1-1.
FULL TEXT  

New Biochemical Markers in Alzheimer Disease
Diaz-Arrastia and Baskin
Arch Neurol 2001;58:354-356.
FULL TEXT