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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 虽然在阿尔茨海默病（AD）中已经广泛证实了β-羟色胺能系统的改变，但5-HT 1A受体的变化从未得到适当的研究。 最近出现的5-HT 1A拮抗剂，可以安全地用于人类现在使这成为可能。 已知5-HT 1A受体与认知和行为有关，这两者在AD中都被破坏。 此外，动物研究表明，5-HT 1A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，重要的是要确定是否5-HT 1A受体在AD和这些变化的幅度和时间过程中被破坏。 因此，我们的目的是确定是否5-HT 1A受体减少，在早期AD使用正电子发射断层扫描（PET）。 招募了10名符合NINCDS-ADRDA标准的轻度至中度AD疑似患者。 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。 同样数量的年龄和性别匹配的控制与完整的认知也从社区招募。 患者和对照组在研究开始前均未接受5-HT 1A特异性药物治疗。 筛选入选后，每组接受10 mCi 5-HT 1A拮抗剂[11 C] WAY 100635静脉注射，然后在注射后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。 除了在组之间使用广泛的感兴趣区域分析（即，双侧额叶、颞叶、顶叶和枕叶皮质的比较）较小区域，例如海马，通过逐像素分析进行比较，以确定是否存在局部差异。 识别AD中的5-HT 1A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。

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.