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Differential chromosome sensitivity to 5-azacytidine in Alzheimer's disease
S L Payão1, M D Smith, P H Bertolucci
1Departamento de Morfologia, Disciplina de Genética, UNIFESP/Escola Paulista de Medicina, São Paulo, Brazil.spepavao.morf@epm.br
Background:
The methylation process in the DNA has been considered a control mechanism of gene activity, connected with genetic imprinting. 5-Azacytidine (5-AZC) is known to be a demethylation agent.
Objective:
We studied the cytogenetic effect of 5-AZC in Alzheimer's disease patients and in two control groups.
Methods:
Peripheral lymphocyte cultures derived from 8 patients with Alzheimer's disease and 8 elderly and 8 healthy young individuals, all female, were studied. The parameters investigated were: the undercondensation of constitutive heterochromatin of chromosomes 1, 9, and 16: the number of lesions in fragile sites 1q42 and 19q13; heterochromatin association, and the total number of induced lesions.
Results:
Our results showed a significantly increased frequency of undercondensation of chromosomes 1, 9, and 16 in Alzheimer's disease patients when compared with elderly and young healthy groups.
Conclusion:
These results suggest that the demethylating action of 5-AZC could reveal differential gene activity in the Alzheimer group at the level of cellular division.