Detection of oxidative DNA damage in lymphocytes of patients with Alzheimer's disease.

Oxidative damage to DNA may play an important role in both normal ageing and in neurodegenerative diseases. The deleterious consequences of excessive oxidations and the pathophysiological role of reactive oxygen species have been intensively studied in Alzheimer's disease. Although the role of oxidative stress in the aetiology of Alzheimer's disease is still not clear, the detection of an increased damage status in the cells of patients could have important therapeutic implications. The levels of oxidative damage in peripheral lymphocytes of 24 Alzheimer's disease patients and of 21 age-matched controls were determined by comet assay applied to freshly isolated blood samples with oxidative lesion-specific DNA repair endonucleases (endonuclease III for oxidized pyrimidines, formamidopyrimidine glycosylase for oxidized purines). It was demonstrated that Alzheimer's disease is associated with elevated levels of oxidized pyrimidines and purines (p<0.0001) as compared with age-matched control subjects. It was also demonstrated that the comet assay is useful as a biomarker of oxidative DNA damage when used with oxidative lesion-specific enzymes.