Gene analysis of the glucocorticoid receptor alpha in Alzheimer's disease.
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.
Department of Biological Chemistry, Medical School, University of Athens, 75 Mikras Asias Street, GR-115 27 Goudi, Athens, Greece.
Amalia F
AF
Tsolakidou
Stavroula A
SA
Coulocheri
George
G
Trikkas
Paraskevi
P
Moutsatsou
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011489:Protein Denaturation; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006728:Hormones; D008024:Ligands; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D006854:Hydrocortisone