Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a common find
ing in Alzheimer's dementia. Since there is loss of hippocampal cortic
osteroid receptors in animal models of aging, and since hippocampal ce
ll loss occurs in Alzheimer's disease (AD), it has been suggested that
a loss of hippocampal glucocorticoid receptors (GR) may underlie some
aspects of HPA axis dysfunction in patients with AD. Levels of cortic
osteroid receptor protein are not reliably determined in postmortem hu
man brain due to rapid lability. In contrast, levels of mRNA coding fo
r GR are stable in postmortem tissue. We report here initial observati
ons from in situ hybridization experiments which indicate that regiona
l levels of glucocorticoid receptor mRNA in hippocampus, as determined
by film autoradiography, are significantly higher in AD hippocampus t
han in controls. While neuronal levels of GR mRNA in AD, revealed by e
mulsion autoradiography, were equal in control and AD tissue. Taken to
gether these results suggest that adrenal dysfunction in AD may relate
to defects in receptor function rather than corticosteroid receptor l
oss in the hippocampus.