FRONTOTEMPORAL DEMENTIA GENES, IMAGES, & EMOTIONS

额颞叶痴呆基因、图像、

• 批准号: 8171026
• 负责人: BRUCE L MILLER
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171026
• 关键词: Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Anterior; Apolipoprotein E; Area; Autopsy; Behavior monitoring; Behavioral; Biostatistics Core; Blood specimen; British Columbia; California; Caregivers; Clinical; Cognitive; Communication; Communities; Comprehension; Computer Retrieval of Information on Scientific Projects Database; Data; Data Analyses; Data Quality; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Early Diagnosis; Emotional; Emotions; Enrollment; Ensure; Ethics; Evaluation; Fellowship; Foxes; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Funding; Genes; Genetic; Grant; Image; Imaging Techniques; Institution; Investigation; Knowledge; Language; Los Angeles; Measures; Medial; Medical; Methods; Monitor; Motor; Neurologic; Neurology; Pathology; Patients; Perfusion; Personality; Policies; Postdoctoral Fellow; Principal Investigator; Procedures; Process; Program Research Project Grants; Progressive Supranuclear Palsy; Proteomics; Reaction; Receptive aphasia; Recruitment Activity; Regulation; Research; Research Infrastructure; Research Personnel; Resources; Scanning; Semantic Dementias; Source; Stimulus; Syndrome; System; Temporal Lobe; Tissues; Training; Ubiquitin; United States National Institutes of Health; Universities; Work; amyloid imaging; base; brain behavior; clinical Diagnosis; cognitive control; cohort; corticobasal degeneration; data management; emotion regulation; frontal lobe; healthy aging; innovation; interest; mRNA Expression; morphometry; neurobehavioral; neuropathology; neuropsychological; novel; patient population; presenilin-1; programs; response; social; tau Proteins

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. This program project grant will determine the imaging, emotional, social-cognitive, language, genetic and diagnostic features of frontotemporal lobar degeneration (FTLD) and related disorders including corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and amyotrophic lateral sclerosis (ALS) in contrast to Alzheimer's disease (AD) and healthy aging. In project 2 we will explore the imaging features of the three major FTLD syndromes and a new cohort of patients with ALS using a 4.0 Tesla magnet. This project will use new imaging techniques including tensor-based morphometry, perfusion and diffusion tensor imaging. In project three we will use methods derived from basic emotion research to evaluate emotional functioning (reactivity, regulation, knowledge) in all three FTLD subtypes compared to AD. Dyads interaction between patients and caregivers, low-level emotion processing and higher order reactions to these basic emotional stimulations will be determined. Project 4 will use all of the information captured through the clinical core, genetics core as well as new amyloid imaging and proteomics parameters to explore better separation of FTLD subtypes from each other and from AD, early diagnosis and better prediction of patients with FTLD-associated tau pathology from those with FTLD-ubiquitin pathology. A new project 5 explores brain-behavior relationships in FTLD using novel and innovative cognitive and social probes. Using 4.0 Tesla scans from project 2 the relationship between changes in the dorsal frontal regions and specific aspects of cognitive control of motor responses and regulation of emotion, the relationship between changes in the ventral and medial prefrontal regions and activation of the emotional systems for monitoring of behavior and the relationship between the anterior temporal lobe and comprehension of verbal and non-verbal stimuli will be explored. Project 1 which was focused upon finding novel genes associated with FTLD is replaced by a Genetics Core that will not only perform routine studies of apolipoprotein E, tau, and presenilin 1, but will also explore mRNA expression of tau-related and frontal lobe related genes. Through the Clincial Core novel assessment of 107 AD, 131 FTD, 67 SD, 56 PNFA, 43 CBD, 30 PSP, 59 ALS, and 89 controls will be completed by year 10. Neuropathology will be completed in 37 AD, 64 FTD, 25 SD, 23 PNFA, 23 CBD, 23 PSP and 27 ALS patients. This PPG represents one of the largest efforts to understand the clinical features of FTLD ever performed. PRINCIPAL INVESTIGATOR: Dr. Miller received his medical and neurologic training at the University of British Columbia. He then completed a post-doctoral fellowship in Behavioral Neurology at the University of California, Los Angeles (UCLA). His interest in Frontotemporal Lobar Degeneration (FTLD) began when he was at UCLA and it continues to be his primary interest. There are few research groups in the world that focus on FTLD, perhaps because it has been so difficult to reconcile its' heterogeneous clinical and neuropathologic presentation. Dr. Miller has assembled an interdisciplinary team of investigators with expertise in the clinical, behavioral, neuropathological, imaging and genetic issues related to FTLD. It is clearly one of the premier groups in the world working in this area. FTLD is an understudied, important and particularly challenging, area of investigation. Taken as a whole, this program project represents one of the best groups in the world attempting to understand and treat this patient population. REVIEW OF THE COMPONENTS CORE A - CLINICAL AND ADMINISTRATIVE; DR. BRUCE L. MILLER DESCRIPTION (provided by applicant): The Clinical and Administrative Core provides essential operational functions for the entire PPG. This Core will recruit patients with frontotemporal dementia (FTD), semantic dementia (SD), progressive non-fluent aphasia (PNFA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and normal control subjects. Each subject will receive a comprehensive evaluation measuring a broad range of neurological, neuropsychological, functional, neurobehavioral, and social-personality variables. In addition, subjects will be followed annually to collect longitudinal data and maintain high enrollment in our autopsy program. Administrative functions of this Core include the infrastructure for establishing policies and procedures, maintaining communication within the PPG and between the PPG and the scientific community, ensuring optimal utilization and monitoring of PPG resources, and ensuring the scientific and ethical integrity of all PPG practices. Once recruited into the Clinical and Administrative Core, subjects will be referred to Projects 2 (Imaging; Dr. Weiner), 3 (Emotion; Dr. Levenson), 4 (Clinical Diagnosis; Dr. Miller), and 5 (Brain-Behavior; Dr. Rosen). In addition, blood samples will be sent to the Genetics Core (Dr. Geschwind) and autopsy tissue will be sent to the Pathology Core (Drs. Trojanowski and Lee). The Clinical and Administrative Core will also interact extensively with the Data Management and Biostatistics Core (Dr. Fox) for data management, data quality, and data analysis functions.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该计划项目拨款将确定额颞叶变性（FTLD）和相关疾病的影像、情感、社会认知、语言、遗传和诊断特征，包括皮质基底节变性（CBD）、进行性核上性麻痹（PSP）和肌萎缩侧索硬化症（ALS），与阿尔茨海默病（AD）和健康老龄化相比。在项目 2 中，我们将使用 4.0 特斯拉磁铁探索三种主要 FTLD 综合征和一组新的 ALS 患者的成像特征。该项目将使用新的成像技术，包括基于张量的形态测量、灌注和扩散张量成像。在项目三中，我们将使用源自基本情绪研究的方法来评估所有三种 FTLD 亚型与 AD 的情绪功能（反应性、调节性、知识）。患者和护理人员之间的二元互动、低级情绪处理和对这些基本情绪刺激的高级反应将被确定。项目 4 将利用通过临床核心、遗传学核心以及新的淀粉样蛋白成像和蛋白质组学参数捕获的所有信息，探索 FTLD 亚型彼此之间以及与 AD 的更好分离，以及 FTLD 相关 tau 病理学患者与 FTLD 泛素病理学患者的早期诊断和更好预测。新项目 5 使用新颖和创新的认知和社会探针探索 FTLD 中的大脑行为关系。使用项目 2 中的 4.0 Tesla 扫描，将探索背侧额叶区域的变化与运动反应和情绪调节的认知控制的特定方面之间的关系，腹侧和内侧前额叶区域的变化与用于监控行为的情绪系统的激活之间的关系，以及前颞叶与言语和非言语刺激的理解之间的关系。专注于寻找与 FTLD 相关的新基因的项目 1 被遗传学核心所取代，该核心不仅将进行载脂蛋白 E、tau 和早老素 1 的常规研究，还将探索 tau 相关和额叶相关基因的 mRNA 表达。通过临床核心，对 107 名 AD、131 名 FTD、67 名 SD、56 PNFA、43 名 CBD、30 名 PSP、59 名 ALS 和 89 名对照患者的新评估将在第 10 年完成。神经病理学将在 37 名 AD、64 名 FTD、25 名 SD、23 PNFA、23 CBD、23 名 PSP 和 27 名 ALS 患者中完成。该 PPG 代表了有史以来为了解 FTLD 临床特征所做的最大努力之一。主要研究者：米勒博士在不列颠哥伦比亚大学接受了医学和神经病学培训。随后，他在加州大学洛杉矶分校 (UCLA) 完成了行为神经学博士后研究。他在加州大学洛杉矶分校时就开始对额颞叶变性 (FTLD) 产生兴趣，并且一直是他的主要兴趣。世界上很少有研究小组关注 FTLD，这可能是因为很难协调其不同的临床和神经病理学表现。 Miller 博士组建了一支跨学科研究团队，他们在 FTLD 相关的临床、行为、神经病理学、影像和遗传问题方面拥有专业知识。它显然是世界上在这一领域开展工作的主要团体之一。 FTLD 是一个研究不足、重要且特别具有挑战性的研究领域。总体而言，该计划项目代表了世界上试图了解和治疗这一患者群体的最佳团体之一。审查核心 A 部分 - 临床和管理；博士。 BRUCE L. MILLER 描述（由申请人提供）：临床和管理核心为整个 PPG 提供基本的运营功能。该核心将招募额颞叶痴呆（FTD）、语义痴呆（SD）、进行性非流利性失语症（PNFA）、进行性核上性麻痹（PSP）、皮质基底节变性（CBD）、肌萎缩侧索硬化症（ALS）、阿尔茨海默病（AD）和正常对照受试者。每个受试者都将接受全面的评估，测量广泛的神经学、神经心理学、功能、神经行为和社会人格变量。此外，每年都会对受试者进行跟踪，以收集纵向数据并保持尸检计划的高注册率。该核心的管理职能包括建立政策和程序的基础设施、维持 PPG 内部以及 PPG 与科学界之间的沟通、确保 PPG 资源的最佳利用和监控，以及确保所有 PPG 实践的科学和道德完整性。一旦被招募到临床和管理核心，受试者将被转介至项目 2（成像；Weiner 博士）、3（情感；Levenson 博士）、4（临床诊断；Miller 博士）和 5（大脑行为；Rosen 博士）。此外，血液样本将被送往遗传学核心（Geschwind 博士），尸检组织将被送往病理学核心（Trojanowski 和 Lee 博士）。临床和管理核心还将与数据管理和生物统计核心（Fox 博士）广泛互动，以实现数据管理、数据质量和数据分析功能。