GLUCOCORTICOID RECEPTOR MESSENGER-RNA IN ALZHEIMERS DISEASED HIPPOCAMPUS

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.