Alzheimer's disease (AD) is a complex progressive neurodegenerative disorder of the brain and is the commonest form of dementia. The prevalence of this disease is predicted to increase 3-fold over the next 30 years and to date no reliable and conclusive diagnostic test exists that will identify individuals presymptomatically of susceptibility risk. This review examines the molecular, genetic, dietary and environmental evidence underlying the known pathology of AD and proposes a biologically plausible chromosome instability model to explain some of the features of the disease. Genome damage biomarkers such as aneuploidy of chromosome 17 and 21, oxidative damage to DNA and telomere shortening together with abnormal expression of APP, beta amyloid and tau proteins are discussed in terms of their potential value as risk biomarkers. These biomarkers could then be used in diagnosis and the evaluation of potentially effective preventative measures.