AMYLOID PLAQUE AND TANGLE IMAGING IN AGING AND DEMENTIA

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 淀粉样老年斑（SP）和神经纤维缠结（NFT）是阿尔茨海默病（AD）的神经病理学标志，也在与正常衰老相关的关键脑区域中积累。我们的小组已经合成了一种小分子探针，2-（1-{6-[（2-[F-18]Fluoroethyl）（methyl）amino]-2-naphthyl}ethylidene）malononitrile（[18 F]FDDNP），其使用荧光显微镜提供了AD脑标本中NFT、SP和弥漫性淀粉样蛋白的良好可视化，并且体内人体正电子发射断层扫描（PET）研究显示[18 F]FDDNP标记AD患者的内侧颞叶皮质。该计划项目资助旨在确定这种斑块和缠结PET成像方法是否（1）与与衰老和痴呆（AD和额颞叶痴呆[FTD]）相关的神经病理学变化的预期积累相关;（2）预测AD风险人群和痴呆患者的未来下降;（3）增强其他信息成像（例如，结构和功能磁共振成像[MRI]、葡萄糖代谢的FDG-PET测量、5-羟色胺受体密度的[18FJMPPF-PET测量）、神经心理学和遗传风险（载脂蛋白E-4 [APOE-4]、tau基因的H1单倍型）测量在正常衰老和痴呆的诊断和鉴别诊断中的应用。一个行政和临床核心，一个化学和PET成像核心，和一个图像分析核心将支持三个拟议的项目：（1）可视化大脑A-β，tau和5-羟色胺受体密度;（2）临床斑块和缠结成像在老龄化和痴呆症;和（3）多模态脑成像在老龄化和痴呆症。该基础设施将提供一个机会，研究转基因动物模型，神经病理学相关性，结合特征，纵向PET，MRI，神经心理学和遗传风险数据在AD和额颞叶痴呆患者，MCI患者，年轻和老年人对照。该项目将扩展AD早期检测和预防的既定计划，旨在（1）识别最有可能从早期干预中受益的前驱患者，（2）提供客观，非侵入性的方法来监测治疗试验。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Amyloid senile plaques (SPs) and neurofibrillary tangles (NFTs) are neuropathological hallmarks of Alzheimer's disease (AD) that also accumulate in key brain regions in association with normal aging. Our group has synthesized a small molecule probe, 2-(1-{6-[(2-[F-18]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP), which provides excellent visualizations of NFTs, SPs, and diffuse amyloid in AD brain specimens using fluorescent microscopy, and in vivo human positron emission tomography (PET) studies show that [18F]FDDNP labels medial temporal cortex in AD patients. This program project grant is designed to determine whether this method of plaque and tangle PET imaging (1) correlates with the expected accumulation of neuropathological changes associated with aging and dementia (AD and frontotemporal dementia [FTD]); (2) predicts future decline in people at risk for AD and in patients with dementia; and (3) augments other informative imaging (e.g., structural and functional magnetic resonance imaging [MRI], FDG-PET measures of glucose metabolism, [18FJMPPF-PET measures of serotonin receptor density), neuropsychological, and genetic risk (apolipoprotein E-4 [APOE-4], H1 haplotype of the tau gene) measures in diagnosis and differential diagnosis of normal aging and dementia. An Administrative and Clinical Core, a Chemistry and PET Imaging Core, and an Image Analysis Core will support three proposed projects: (1) Visualizing brain A-beta, tau and serotonin receptor densities; (2) Clinical plaque and tangle imaging in aging and dementia; and (3) Multi-modal brain imaging in aging and dementia. This infrastructure will provide an opportunity to study transgenic animal models, neuropathological correlations, binding characteristics, and longitudinal PET, MRI, neuropsychological and genetic risk data in patients with AD and frontotemporal dementia, people with MCI, and younger and older adult controls. This project will expand an established program in early detection and prevention of AD, designed (1) to identify presymptomatic persons most likely to benefit from early intervention and (2) to provide an objective, noninvasive means to monitor therapeutic trials.