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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 尽管阿尔茨海默病 (AD) 中血清素能系统的改变已得到广泛证实，但 5-HT1A 受体的变化从未得到适当的研究。 最近出现的可安全用于人类的 5-HT1A 拮抗剂使这成为可能。 已知 5-HT1A 受体与认知和行为有关，而这两者在 AD 中都会受到干扰。 此外，动物研究表明，5-HT1A 拮抗剂可能通过调节谷氨酸能系统在 AD 中发挥治疗作用。 因此，确定 5-HT1A 受体在 AD 中是否受到破坏以及这些变化的程度和时间进程非常重要。 因此，我们的目的是使用正电子发射断层扫描 (PET) 确定早期 AD 中 5-HT1A 受体是否减少。 招募了 10 名符合 NINCDS-ADRDA 标准的可能患有 AD 且具有轻度至中度症状的患者。 所有患者都将接受全面的神经精神评估，包括一般功能能力、认知功能和非认知功能的测量。 还从社区招募了同等数量的年龄和性别匹配且认知完整的对照组。 在研究开始之前，患者和对照组均未服用 5-HT1A 特异性药物。 筛选纳入后，每组均静脉注射 10mCi 5-HT1A 拮抗剂 [11C] WAY100635，注射后 75 分钟进行 PET 扫描。 受试者和对照组都接受了与 PET 扫描共同配准的 MRI 扫描。 MRI 用于确定感兴趣区域的位置并调整参与者的脑萎缩情况。 除了使用组间广泛的感兴趣区域分析（即比较双侧额叶、颞叶、顶叶和枕叶皮质）之外，还通过逐像素分析比较较小的区域，例如海马体，以确定局部区域是否存在差异。存在差异。 识别 AD 中的 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。