A POSITRON EMISSSION TOMOGRAPHY STUDY OF 5-HT1A RECEPTORS IN ALZHEIMER'S DISEASE

阿尔茨海默病 5-HT1A 受体的正电子发射断层扫描研究

• 批准号: 8171132
• 负责人: Krista L. Lanctot
• 金额: $ 1.22万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171132
• 关键词: Activities of Daily Living; Age; Alzheimer' s Disease; Animals; Area; Behavior; Bilateral; Cognition; Communities; Computer Retrieval of Information on Scientific Projects Database; Functional disorder; Funding; Grant; Human; Injection of therapeutic agent; Institution; Location; MRI Scans; Magnetic Resonance Imaging; Measures; Occipital lobe; Parietal; Participant; Patients; Pharmaceutical Preparations; Play; Positron; Positron-Emission Tomography; Recruitment Activity; Research; Research Personnel; Resources; Role; Screening procedure; Serotonin Receptor 5-HT1A; Source; System; Therapeutic; Time; United States National Institutes of Health; cerebral atrophy; cognitive function; interest; intravenous injection; meetings; neuropsychiatry; receptor; sex; therapeutic target; tomography

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although alterations in the serotonergic system have been broadly demonstrated in Alzheimer's disease (AD), changes in the 5-HT1A receptor has never been properly studied. The recent emergence of 5-HT1A antagonists that can be safely used in humans now makes this possible. The 5-HT1A receptor is known to be involved with cognition and behaviour, both of which are disrupted in AD. Furthermore, animal studies suggest that 5-HT1A antagonists may play a therapeutic role in AD via modulation of the gluatmatergic system. As a result, it is important to ascertain whether or not 5-HT1A receptors are disrupted in AD and the magnitude and time course of these changes. Therefore, we aimed to determine if 5-HT1A receptors are decreased in early AD using positron emission tomography (PET). Ten patients who meet NINCDS-ADRDA criteria for probable AD with mild to moderate symptomatology were recruited. All patients will had a full neuropsychiatric assessment that includes measures of general functional capacity, cognitive function and noncognitive function. An equal number of age- and sex-matched controls with intact cognition were also recruited from the community. Patients and controls were free from 5-HT1A-specific medications prior to initiation of the study. After screening for inclusion, each group was administered a 10mCi intravenous injection of the 5-HT1A antagonist, [11C] WAY100635, followed by a PET scan 75 minutes post-injection. Both subjects and controls also underwent an MRI scan that was co-registered with the PET scan. The MRI was be used to determine the location of the regions of interest and to adjust for brain atrophy in the participants. In addition to using a broad region of interest analysis between groups (i.e., comparison of bilateral frontal, temporal, parietal and occipital cortices) smaller areas, such as the hipppocampus, was be compared through a pixel-by-pixel analysis to determine whether local differences exist. Identifying 5-HT1A dysfunction in AD is the first step in elucidating the role of this system in AD and determining its potential as a therapeutic target.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 尽管在阿尔茨海默氏病（AD）中广泛证明了血清素能系统的改变，但从未正确研究5-HT1A受体的变化。 现在可以安全地在人类中安全使用的5-HT1A拮抗剂的最近出现使这成为可能。 已知5-HT1A受体与认知和行为有关，两者在AD中都被破坏。 此外，动物研究表明，5-HT1A拮抗剂可以通过调节GluatMatergic系统在AD中发挥治疗作用。 结果，重要的是确定在AD中是否破坏了5-HT1A受体以及这些变化的幅度和时间过程。 因此，我们旨在使用正电子发射断层扫描（PET）确定早期AD中的5-HT1A受体是否降低。 招募了符合NINCDS-ADRDA标准的十名患者，该标准招募了可能具有轻度至中度症状的AD。 所有患者将进行全面的神经精神病学评估，其中包括一般功能能力，认知功能和非认知功能的度量。 还从社区招募了相等数量的具有完整认知的年龄和性别匹配的对照。 在开始研究之前，患者和对照组没有5-HT1A特异性药物。 筛选纳入后，每组均进行5-HT1A拮抗剂的10mCi静脉注射[11C] Way100635，然后在注射后75分钟进行PET扫描。 受试者和对照组还进行了与PET扫描共同注册的MRI扫描。 MRI用于确定目标区域的位置并调整参与者中的脑萎缩。 除了使用群体之间的广泛分析区域（即比较双侧额叶，颞叶，顶叶和枕皮层）较小区域（例如河马）外，还可以通过像素的像素分析进行​​比较，以确定是否存在局部差异。 在AD中识别5-HT1A功能障碍是阐明该系统在AD中的作用并确定其作为治疗靶点的潜力的第一步。