DECREASED PERIPHERAL GLUCOCORTICOID SENSITIVITY IN ALZHEIMERS-DISEASE

Both peripheral and central glucocorticoid sensitivity was examined in patients with Alzheimer's disease (AD; n = 3), glucocorticoid-treated patients (n = 8), healthy elderly controls (n = 10) and young control s (n = 9). We performed glucocorticoid receptor-mediated skin vasocons trictor responses to clobetasol and low-dose dexamethasone suppression tests. Patients with AD showed skin blanching at a significantly high er clobetasol concentration than did healthy elderly controls (p = 0.0 02). There was no difference in skin blanching between patients with A D and patients treated with corticosteroids. Patients with AD had sign ificantly higher post-dexamethasone serum cortisol levels than healthy elderly (p = 0.01). No association was found between skin blanching a nd dexamethasone suppressibility. Thus patients with AD have apparentl y independent reductions in both central nervous system and peripheral glucocorticoid sensitivity. These results predict an increase in gluc ocorticoid secretion in some patients, which might accelerate neuronal degeneration in the absence of features of overexposure to glucocorti coids in peripheral tissues.