Glucocorticoid receptor mRNA in Alzheimer's diseased hippocampus

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction is a common finding in Alzheimer's dementia. Since there is a loss of hippocampal corticosteroid receptors in animal models of aging, and since hippocampal cell 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 corticosteroid receptor protein are not reliably determined in postmortem human brain due to rapid lability. In contrast, levels of mRNA coding for GR are stable in postmortem tissue. We report here initial observations from in situ hybridization experiments which indicate that regional levels of glucocorticoid receptor mRNA in hippocampus, as determined by film autoradiography, are significantly higher in AD hippocampus than in controls. While neuronal levels of GR mRNA in AD, revealed by emulsion autoradiography, were equal in control and AD tissue. Taken together these results suggest that adrenal dysfunction in AD may relate to defects in receptor function rather than corticosteroid receptor loss in the hippocampus.