BETA ADRENERGIC RECEPTORS IN ALZHEIMER'S DISEASE

阿尔茨海默氏病（AD）与几种阿尔茨海默氏病中的神经元损失有关。 神经递质系统，包括去甲肾上腺素系统，在大脑中。 蓝斑神经元的缺失可能导致突触后改变 在特定区域的β肾上腺素能受体（BAR）人群中， 可能反过来导致疾病的表现。 本 本研究的目的是研究神经解剖学的分布和亚型 在死后条件下，与AD相关的BAR变化的特异性。 AD的局部效应将通过体外受体研究 AD患者脑切片的放射自显影与年龄和性别 尸检后获得的匹配对照，充分代表 性别 只有无药物和无神经病理学的大脑将被纳入 对照组 AD组由使用以下方法诊断的患者组成： NINCDS-ADRDA标准，诊断确认基于 脑组织病理学检查死后。 总酒吧将是 使用150 pM 125 I-碘吲哚洛尔进行评估。 β 1结合将在 存在100 nM锌特罗（一种选择性β 2阻滞剂）和β 2 受体将在100 nM美托洛尔存在下可视化， 选择性β 1因子。 非特异性结合是在以下物质存在下测量的： 1000 nM普萘洛尔。 BAR的区域变化将与 个体AD患者的各种临床特征， 了解这些变化对频谱的贡献 AD中出现的神经行为异常

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.