Background: In Alzheimer's disease (AD), the hypothalamic-pituitary-adrenal (HPA) axis is hyperactive and the sensitivity to dexamethasone is decreased, suggesting a possible involvement of glucocorticoid receptor alpha (GRalpha) defects in the aetiopathology of the disease.
Methods: We, therefore, searched for the presence of mutations in the human GRalpha (hGRalpha) gene, focusing on the hormone-binding domain due to its importance in mediating glucocorticoids' effects. RNA isolated from peripheral blood mononuclear cells (PBMCs) of 15 patients with Alzheimer's disease and 20 healthy individuals was subjected to reverse transcription-polymerase chain reaction amplification (RT-PCR) analysis followed by denaturing gradient gel electrophoresis (DGGE).
Results: No mutations could be detected in the region of the hGRalpha gene examined.
Conclusions: We conclude that the hormone-binding domain of GRalpha is not altered in Alzheimer's disease and molecular defects in other gene regions of the GRalpha or in its isoform GRbeta warrant further investigation in Alzheimer's disease.