BETA ADRENERGIC RECEPTORS IN ALZHEIMER'S DISEASE

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Alzheimer's disease (AD) is associated with neuronal losses in several neurotransmitter systems, including the noradrenergic system, in the brain. Loss of neurons in the locus coeruleus may result in postsynaptic changes in beta adrenergic receptor (BAR) populations in specific regions, which may in turn contribute to the manifestations of the disease. The present proposal is designed to study the neuroanatomical distribution and subtype specificity of changes in BAR related to AD under postmortem conditions. The regional effects of AD will be studied by in vitro receptor autoradiography on sections from brains of AD patients and age- and sex matched controls obtained postmortem, with adequate representation of both sexes. Only drug- and neuropathology-free brains will be included in the control group. The AD group is composed of patients diagnosed using NINCDS-ADRDA criteria with a confirmation of the diagnosis based on histopathological examination of the brain postmortem. Total BAR will be assessed using 150 pM 125I-iodopindolol. Beta1 binding will be examined in the presence of 100nM Zinterol, a selective beta2 blocker, and beta2 receptors will be visualized in the presence of 100nM metoprolol, a selective beta1 agent. Non specific binding is measured in the presence of 1000nM propranolol. Regional changes in BAR will be correlated with various clinical features of individual AD patients in an attempt to understand the contribution of these changes to the spectrum of neurobehavioral abnormalities seen in AD.