AMYLOID PLAQUE AND TANGLE IMAGING IN AGING AND DEMENTIA

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 淀粉样老年斑 (SP) 和神经原纤维缠结 (NFT) 是阿尔茨海默病 (AD) 的神经病理学标志，它们也会在与正常衰老相关的关键大脑区域中积累。我们的小组合成了一种小分子探针2-(1-{6-[(2-[F-18]氟乙基)(甲基)氨基]-2-萘基}亚乙基)丙二腈([18F]FDDNP)，它可以使用荧光显微镜对AD脑标本中的NFT、SP和弥漫性淀粉样蛋白进行良好的可视化，并且体内人体正电子发射断层扫描(PET)研究表明[18F]FDDNP 标记 AD 患者的内侧颞叶皮层。该计划项目拨款旨在确定这种斑块和缠结 PET 成像方法 (1) 是否与与衰老和痴呆（AD 和额颞叶痴呆 [FTD]）相关的神经病理变化的预期累积相关； (2) 预测 AD 风险人群和痴呆症患者的未来下降； (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、血清素受体密度的 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作用。行政和临床核心、化学和 PET 成像核心以及图像分析核心将支持三个拟议项目：(1) 可视化大脑 A-β、tau 和血清素受体密度； (2) 衰老和痴呆的临床斑块和缠结成像； (3) 衰老和痴呆症的多模式脑成像。该基础设施将为研究 AD 和额颞叶痴呆患者、MCI 患者以及年轻人和老年人对照的转基因动物模型、神经病理学相关性、结合特征以及纵向 PET、MRI、神经心理学和遗传风险数据提供机会。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症状前人群，以及 (2) 提供客观、非侵入性的手段来监测治疗试验。

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.