IN VIVO AMYLOID AND DEMENTIA IN SYNUCLEIONOPATHIES

突触核蛋白病中的体内淀粉样蛋白和痴呆

• 批准号: 6887218
• 负责人: ROBERT Y. MOORE
• 金额: $ 9.88万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6887218
• 关键词: Alzheimer' s disease; Lewy body; Parkinson' s disease; alpha synuclein; amyloid proteins; clinical research; dementia; human subject; magnetic resonance imaging; neural degeneration; neuropathology; neuropsychological tests; pathologic process; positron emission tomography

Synucleinopathies are now recognized as major causes of dementia. The principal synucleinopathies are the overlapping clinical entities of Parkinson disease (PD), including Parkinson disease with dementia (PDD), and dementia with Lewy bodies (DLB). PDD and DLB are the most common causes of dementia after Alzheimer disease (AD). A clinical distinction between PDD and DLB, and distinguishing them from AD, is often difficult and, perhaps more importantly, the clinician encounters many situations in which it is unclear from clinical data and structural imaging whether a dementia reflects predominantly a single process or a complex one with Alzheimer changes coexisting with one or more of the other pathologies. In addition, as more specific therapies become available, it will be important to have methods to distinguish among the contributing pathological processes. The intent of this project is to use amyloid PET (PIB PET) combined with Clinical and neuropsychological evaluation, fluorodeoxyglucose (FDG) PET and dopamine transporter PET (in DLB ) to determine the contribution of amyloid deposition to dementia in PD and DLB. The specific aims are as follows: 1) to perform PIB PET in DLB and PDD subjects that have been carefully characterized with respect to clinical features, changes on structural MRI, PD rating scales, neuropsychological performance, FDG PET and DAT PET (DLB); 2) to perform PIB PET at study entry and after 3 years in PD subjects characterized at both time points with respect to clinical features, PD rating scales, changes on structural MRI, neuropsychological performance and FDG PET. The overall objectives of the project are to determine the following: 1) the contribution of beta-amyloid accumulation to the dementia in PDD and DLB; 2) the role of beta-amyloid accumulation in the conversion of PD to PDD; 3) the contribution of FDG, PIB PET and dopamine transporter PET, correlated with clinical evaluation, neuropsychological testing and structural imaging, to understanding the pathophysiology of dementia associated with synucleinopathies.

突触核酸现在被认为是痴呆症的主要原因。主要突触核苷是帕金森氏病（PD）的重叠临床实体，包括患有痴呆症（PDD）的帕金森氏病（PDD）和带有Lewy身体（DLB）的痴呆症。 PDD和DLB是阿尔茨海默氏病（AD）后最常见的痴呆症原因。 PDD和DLB之间的临床区别通常很困难，也许更重要的是，临床医生会遇到许多情况，从临床数据和结构性成像中尚不清楚痴呆症是否主要反映了单一过程还是与阿尔茨海默氏症的变化相关的一部分是与一种或更多的一种方法相关的过程。另外，AS 更具体的疗法可用，具有区分促进病理过程的方法将很重要。该项目的目的是使用淀粉样蛋白PET（PIB PET），结合临床和神经心理学评估，氟脱氧葡萄糖（FDG）PET和多巴胺转运蛋白PET（在DLB中）来确定PD和DLB中淀粉样蛋白对痴呆症的贡献。具体目的如下：1）在DLB和PDD受试者中执行PIB PET，这些受试者在临床特征，结构MRI的变化，PD等级量表，神经心理学表现，FDG PET和DAT PET（DLB）方面进行了仔细的特征； 2）在研究进入时进行PIB PET，并在PD受试者中进行3年后，在两个时间点都在临床特征，PD等级量表，结构MRI的变化，神经心理学性能和FDG PET方面进行了PD受试者。该项目的总体目标是 确定以下内容：1）β-淀粉样蛋白积累对PDD和DLB中痴呆的贡献； 2）β-淀粉样蛋白积累在PD转化为PDD中的作用； 3）FDG，PIB PET和多巴胺转运蛋白PET的贡献与临床评估，神经心理学测试和结构成像相关，以理解与突触核肺肺泡有关的痴呆症的病理生理学。