Homocysteine may contribute to pathogenesis of RNA damage in brains with Alzheimer's disease

Abstract

Background: The pathogenesis of Alzheimer's disease (AD) is related to homocysteine (HC), but the details are unknown. Objective: We aimed to measure the cerebrospinal fluid (CSF) concentrations of 8-hydroxyguanosine (8-OHG), considering RNA oxidative damage marker, free HC and total HC in the CSF of patients with AD and in normal control subjects. Method and Patients: Subjects were 18 untreated patients with AD (M/F = 7/11) and 15 age-matched controls (M/F = 9/6), with a mean age ± SD of 67.4 ± 5.0 years for patients and of 65.7 ± 9.2 years for controls. The concentrations of free HC, total HC and 8-OHG in the CSF of AD patients were measured by high-performance liquid chromatography using an electrochemical detector. The control subjects were neurologically normal patients who underwent lumbar spinal anesthesia for minor surgery. Results: Total HC and 8-OHG concentrations were significantly increased, and there was a significant positive correlation between total HC and 8-OHG concentrations. However, the concentration of 8-OHG in the CSF showed no correlation with 8-OHG in serum and was not significantly altered in AD patients. Conclusion: These results suggest that total HC and 8-OHG are positively correlated and may be related to AD pathogenesis due to RNA-associated oxidative damage linked to total HC. Copyright © 2009 S. Karger AG.