The contribution of oxidative stress to neurodegeneration is not peculiar of a specific neurodegenerative disease, oxidative stress has been found implicated in a number of neurodegenerative disorders among which Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS). Even increasing are studies dealing with the search for peripheral biomarkers of oxidative stress in biological fluids or even in peripheral tissues themselves such as fibroblasts or blood cells. The application of the modified version of the comet assay for the detection of oxidised purines and pyrimidines in peripheral blood leukocytes results particularly useful if the study requires repeated blood drawn from the same individual, for instance if a clinical trial is performed with a preventive therapy. Likely damage occurs to every category of biological macromolecules and we consider, in the context of neurodegenerative diseases, particularly critical the proteic level. The identification of subjects at risk to develop AD or with pre-pathogenic conditions, the possibility to use "a battery of assays" for the detection of oxidative damage at peripheral level, together with recent advances in brain imaging, will allow to better address studies aimed not only to therapeutic purposes but also mainly to primary prevention.