EMISSION COMPUTED TOMOGRAPHY OF LOCAL CEREBRAL FUNCTION

局部脑功能的发射计算机断层扫描

• 批准号: 2839319
• 负责人: DAVID E KUHL
• 金额: $ 45.98万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2839319
• 关键词: Alzheimer's disease; Lewy body; Macaca; Parkinson's disease; acetylcholinesterase; bioimaging /biomedical imaging; brain disorder diagnosis; brain imaging /visualization /scanning; brain mapping; brain metabolism; cholinesterase inhibitors; clinical research; diagnosis design /evaluation; early diagnosis; enzyme deficiency; glucose metabolism; human subject; laboratory mouse; laboratory rat; longitudinal human study; membrane transport proteins; positron emission tomography; single photon emission computed tomography

DESCRIPTION: (Adapted from the applicant's abstract) The goals of this project are to determine, with in vivo emission tomography, the temporal and spatial sequence of declines in cerebral cholinergic enzyme activity and cholinergic terminal integrity in patients suspected of early Alzheimer s disease (AD) and in Parkinson s disease (PD), with and without dementia, and to correlate these neuronal biochemical alterations with associated cognitive declines. Hypotheses to be tested include: 1) in normal aging, AD, and PD, patterns differ, but cholinergic enzyme loss always precedes and exceeds cholinergic terminal loss both in severity and in extent; 2) in patients suspected of early AD, those with cholinergic enzyme deficits will progress to AD and those without enzyme deficits will not; and 3) patients with early AD who have the most severe temporal cholinergic deficits and occipital hypometabolism also have the premortem clinical criteria and neuro-psychological profile which have been attributed to Diffuse Lewy Body Disease (DLBD). These issues are difficult to establish with postmortem examinations due to the lack of tissue from early disease. Emission tomography studies using radioactive ligand markers of the presynaptic vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) substrate utilization are proposed in well characterized controls and patients. In parallel with these imaging studies, the development of a new AChE-inhibitor ligand is proposed. This agent will be evaluated in small animal and primate studies in preparation for radiotracer pharmacokinetic evaluation in humans. Success in these efforts is expected to aid the early differential diagnosis of dementing disorders and to provide new insights into the basic pathophysiology of these diseases. Such information could facilitate new pharmacologic classifications of patients, better matches of patients to therapies, more rational pathways to new drugs, and guides to new therapies and strategies for neuroprotection.

描述：（改编自申请人的摘要） 项目是确定，在体内发射断层扫描，时间和 脑胆碱能酶活性下降的空间顺序， 疑似早期阿尔茨海默病患者的胆碱能末梢完整性 在患有和不患有痴呆的帕金森病（PD）中，以及 将这些神经元生化改变与相关的 认知能力下降 待检验的假设包括：1）在正常老化中， AD和PD的模式不同，但胆碱能酶的损失总是先于和 在严重程度和范围上超过胆碱能终末损失; 2）在 对于怀疑早期AD的患者，那些胆碱能酶缺乏的患者将 进展为AD和那些没有酶缺陷的患者不会;和3）患者 患有早期AD的患者，他们具有最严重的颞胆碱能缺陷， 枕骨代谢低下也有生前临床标准， 神经心理学特征归因于弥漫性路易体 疾病（DLBD）。 这些问题很难通过尸检来确定 由于缺乏早期疾病的组织而无法进行检查。 发射 使用突触前的放射性配体标记物的断层摄影研究 囊泡乙酰胆碱转运体（VAChT）和乙酰胆碱酯酶（AChE） 在充分表征的对照中提出了底物利用率， 患者 在这些成像研究的同时，开发了一种新的 提出了乙酰胆碱酯酶抑制剂配体。 该代理将在小 放射性示踪剂药代动力学准备的动物和灵长类动物研究 人类的评价。 预计这些努力的成功将有助于 痴呆症的鉴别诊断并提供新的见解 这些疾病的基本病理生理学。 此类信息可 促进患者的新药理学分类，更好地匹配 患者的治疗，更合理的途径，新的药物，并指导， 神经保护的新疗法和策略。