AMYLOID PLAQUE AND TANGLE IMAGING IN AGING AND DEMENTIA

衰老和痴呆症中的淀粉样斑块和缠结成像

• 批准号: 8363428
• 负责人: GARY William SMALL
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363428
• 关键词: Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Animal Model; Binding; Brain; Brain imaging; Brain region; Characteristics; Chemistry; Clinical; Data; Dementia; Diagnosis; Differential Diagnosis; Diffuse; Early Diagnosis; Early treatment; Elderly; Frontotemporal Dementia; Functional Magnetic Resonance Imaging; Funding; Future; Genes; Genetic Risk; Grant; Haplotypes; Human; Image; Image Analysis; Imagery; Label; Magnetic Resonance Imaging; Measures; Medial; Methods; Microscopy; Modeling; Monitor; National Center for Research Resources; Neurofibrillary Tangles; Patients; Persons; Positron-Emission Tomography; Principal Investigator; Program Research Project Grants; Research; Research Infrastructure; Resources; Senile Plaques; Source; Specimen; Temporal Lobe; Therapy Clinical Trials; Transgenic Animals; United States National Institutes of Health; apolipoprotein E-4; computational anatomy; cost; design; dicyanmethane; glucose metabolism; in vivo; longitudinal positron emission tomography; neuropsychological; normal aging; programs; receptor density; serotonin receptor; small molecule; tau Proteins; young adult

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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。