Endocrinology and Alzheimer's disease.

New concepts in the rapidly expanding field of endocrinology must be elucidated to benefit from the extensive research of the neuro-immuno-endocrine network. In order to place these advances in a proper perspective is necessary to widen the scope of classical endocrinology. In Alzheimer's disease (AD) the main changes in the endocrine system result from a longstanding activation of the HPA-axis due to permanent stress. The final effect of this prolonged hypercortisolism is a neurotoxic damage to the hippocampus which is the key regulator of the HPA system. The task of the hippocampus within the neuroendocrinological network is to stop exaggerating stress response. However, persistent downregulations of the corticoid receptors in the hippocampus will disrupt the negative feedback and lead to further increase in corticosteroids (''glucocorticoid cascade hypothesis''). On the other hand the hippocampus is an important region of memory storage and processing, deficits of which represent key features of AD; thus, a serious hippocampal neuronal loss, qualitatively different to normal aging, is one of the main features of AD. DHEA represents the androgen hormone of the adrenal cortex and its gradual decrease covering the entire span of life has generally been accepted in normal human aging which cortisol levels remaining unchanged. However, in AD this decrease in DHEA serum and CSF concentrations is far more pronounced; thus, the potent antiglucorticoid effects of DHEA is vanishing. It must be stated that DHEA is nor only produced peripherally but also within the CNS and additionally, in the brain there are specific receptors for this ''neurosteroid''. Clinically the DHEA/cortisol ratio may be used as a marker in those AD-patients who are prone to neurotoxic glucocorticoid effects. Thyroid diseases have been observed prior to AD significantly more frequently than in controls. Patients with Down's syndrome, a condition often associated with hypothyroidism or thyroid autoantibodies, inevitably end up with AD. The genetic location of Down's syndrome, familial ADI and amyloid precursor protein, are closely adjoining along chromosome 21. In treatment of AD the cholinergic effect of high doses of TRH was utilized for a number of years. Transthyretin the main thyroxine transport protein in CSF was supposed to be associated with amyloid formation.