The purpose of this project is to examine pharmacological and neurochemical markers of cholinergically mediated sweating in human subjects. Studies will be done in both healthy young and old subjects as well as in individuals suffering from Alzheimer's disease (AD) and a related disorder, Down's Syndrome (DS). These studies are designed to increase our understanding of the basic mechanisms that control the human eccrine sweat gland's response to its sympathetic cholinergic innervation and to extend our knowledge of cholinergic deficits in AD and DS. Quantitative autoradiography will be used to characterize and measure, both eccrine sweat gland muscarinic receptors and presynaptic cholinergic innervation. These biochemical measures of dermal cholinergic function will be correlated with in vivo measures of eccrine sweat gland sensitivity to intradermal injections of carbachol (a muscarinic agonist) and choline (a acetylcholine precursor). Previous reports of sex, age and AD related deficits in cholinergic sensitivity of eccrine sweat glands will be examined and their relationship to changes in eccrine gland muscarinic receptors and sympathetic innervation will be evaluated. Ultimately the goals of this project are (1) to clarify the neurochemical mechanisms controlling cholinergically stimulated sweating and (2) hopefully define a diagnostic marker for AD. To this end, any changes found in dermal cholinergic function will be evaluated for the degree to which they are correlated with the severity of dementia found in AD subjects or are associated with early or late onset AD.