Preferential occurrence of chromosome 21 malsegregation in peripheral blood lymphocytes of Alzheimer disease patients

To further investigate our finding of high levels of spontaneous aneuploidy in somatic cells of Alzheimer's disease (AD) patients (Migliore et al. 199 7), we studied the molecular cytogenetics of eight patients with sporadic A D and six healthy controls of similar age. Cytochalasin B-blocked binucleat ed peripheral blood lymphocytes from the AD patients and unaffected control s were used to measure micronucleus induction or other aneuploidy events, s uch as the presence of malsegregation in interphase nuclei (representing ch romosome loss and gain). Dual-color fluorescence in situ hybridization (FIS H) with differential labeled DNA probes was applied. We used a probe specif ic for the centromeres of chromosomes 13 and 21 combined with a single cosm id for the Down's syndrome region (21q22.2) to obtain information on sponta neous chromosome loss and gain frequencies for both chromosomes (13 and 21) . FISH data showed that AD lymphocytes had higher frequencies of chromosome loss (evaluated as fluorescently labeled micronuclei) for both chromosomes , as well as higher frequencies of aneuploid interphase nuclei, again invol ving both chromosomes, compared to control lymphocytes. However, aneuploidy for chromosome 21 was more frequent than for chromosome 13 in AD patients. This preferential occurrence of chromosome 21 in malsegregation in somatic cells of AD patients raises the hypothesis that mosaicism for trisomy of c hromosome 21 could underlie the dementia phenotype in AD patients, as well as in elderly Down's syndrome patients. Copyright (C) 1999 S. Karger AG, Ba sel.