AMYLOID PLAQUE AND TANGLE IMAGING IN AGING AND DEMENTIA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 淀粉样老年斑(SPS)和神经原纤维缠结(NFTs)是阿尔茨海默病(AD)的神经病理特征，与正常衰老相关，也聚集在关键的大脑区域。我们团队合成了一种小分子探针2-(1-{6-[(2-[F-18]Fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile([18F]FDDNP)，它可以使用荧光显微镜对AD大脑标本中的NFT、SP和弥漫性淀粉样蛋白进行出色的可视化，在活体人类正电子发射断层扫描(PET)研究表明，[18F]FDDNP标记AD患者的内侧颞叶皮质。该计划项目拨款旨在确定这种斑块和缠结PET成像方法(1)是否与预期积累的与衰老和痴呆(AD和额颞叶痴呆[FTD])相关的神经病变相关；(2)预测AD风险人群和痴呆症患者的未来下降；以及(3)增加了其他信息性成像(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)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成像核心和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)老龄化和痴呆症的临床斑块和缠绕成像；(3)老龄化和痴呆症的多模式脑成像。这一基础设施将提供一个机会，研究转基因动物模型、神经病理相关性、结合特征，以及AD和额颞叶痴呆患者、MCI患者以及年轻人和老年人对照组的纵向PET、MRI、神经心理学和遗传风险数据。该项目将扩大已建立的AD早期检测和预防计划，旨在(1)识别最有可能从早期干预中受益的症状前患者，(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. 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. 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.