Micronuclei (MNi) can originate either from chromosome breakage or chromosome malsegregation events and are therefore ideal biomarkers to investigate genomic instability. Studies in peripheral lymphocytes of patients with neurodegenerative diseases, mainly Alzheimer's disease (AD) and Parkinson's disease (PD), revealed an increased micronucleus (MN) frequency in both disorders but originating mainly from chromosome malsegregation events in AD and from chromosome breakage events in PD. Studies in other neurodegenerative diseases are largely missing, and some data in premature ageing disorders characterised by neurodegeneration and/or neurological complications, such as Ataxia telangiectasia, Werner's syndrome, Down's syndrome (DS) and Cockayne's syndrome, indicate that MNi increase with ageing in cultured cells. An increased frequency of aneuploidy characterises several tissues of AD patients, as well as of individuals at increased risk to develop AD, such as mothers of DS individuals and DS subjects themselves. The use of the buccal MN cytome assay in AD and DS subjects allowed finding significant changes in the MN frequency as well as other cellular modifications reflecting reduced regenerative capacity compared to age- and gender-matched controls. These changes in buccal cytome ratios may prove useful as potential future diagnostics to identify individuals of increased risk for these disorders.