SPONTANEOUS AND INDUCED ANEUPLOIDY IN PERIPHERAL-BLOOD LYMPHOCYTES OFPATIENTS WITH ALZHEIMERS-DISEASE

This study was aimed at assessing whether peripheral blood lymphocytes of patients with Alzheimer's disease (AD) show significant levels of aneuploidy and high percentages of cytogenetic events in vitro, indica ting a predisposition to aneuploidy spontaneously, or after chemical t reatment in vitro. A group of affected individuals and a group of unaf fected, age-, sex- and smoking-habit-matched controls were identified. Lymphocytes were cultured for analysis of the following cytogenetic p arameters: premature centromere division (PCD), satellite associations of acrocentric chromosomes (SA) and micronuclei (MN). In a subset of subjects, the fluorescence in situ hybridization (FISH) technique was combined with the MN assay, by means of a pancentromeric DNA probe for the detection of the presence of centric material. To evaluate the se nsitivity to aneuploidogenic agents, in vitro treatment of lymphocytes of affected individuals was performed by adding griseofulvin, a chemi cal whose supposed target is microtubule-associated protein(s). Both t he spontaneous frequency of MN and the frequency of PCD was significan tly higher in patient cells than in controls. Furthermore, after appli cation of the FISH technique, we found that the majority of MN were co mposed of whole chromosomes (because of the phenomenon of chromosome l oss). Metaphase analysis for the detection of associative events betwe en satellite regions of acrocentric chromosomes showed no differences between the two groups under study. Analysis of sensitivity to the ane uploidogen griseofulvin showed that the patient group was characterize d by lower levels of MN induction compared with controls. Our data con firm that peripheral blood lymphocytes of AD patients are prone to und ergo aneuploidy spontaneously in vitro and support the hypothesis that microtubule impairment might be associated with the disease.