Effect of Vitamin E Administration on the Elevated Oxygen Stress and the Telomeric and Subtelomeric Status in Alzheimer’s Disease

Background: Oxidative stress (OS) may be involved in the neurodegenerative process in Alzheimer’s disease (AD). Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, are sensitive to OS, and serve as markers of a cell’s replicative history. Telomere length shortening has been reported to relate to OS with aging process and aging-associated diseases, but the telomeric changes were not always identical, especially in change of telomere length distribution and subtelomeric methylation. The involvement of an OS-associated telomere change in the pathogenesis of AD has been discussed for decades, and the telomere length and telomerase activity were analyzed. However, other telomeric factors, such as the telomere distribution and subtelomeric methylation status, have not yet been analyzed. Objective: The subtelomeric methylation status as well as the telomere length were studied in AD with an antioxidant vitamin in terms of OS. Methods: We measured urinary 8-iso-PGF2α, a lipid-peroxidation product as an OS marker, and methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells by Southern blotting in AD patients before and after vitamin E treatment. Results: The level of urinary 8-iso-PGF2α was found to have increased in AD. Middle-ranged telomeres (4.4–9.4 kb) increased and the shortest telomeres (