FRONTOTEMPORAL DEMENTIA GENES, IMAGES, & EMOTIONS

额颞叶痴呆基因、图像、

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此，可以在其他清晰的条目中表示。列出的机构是对于中心，这不一定是调查员的机构。该计划项目赠款将确定额颞Lobar变性（FTLD）的成像，情感，社交认知，语言，遗传和诊断特征（FTLD）和相关疾病，包括皮质性Bassal变性（CBD），进行性进行性促进性核上麻痹（PSP）（PSP）和amyotrophic sperlophic coplorisis（Als））与阿尔茨海默氏病（AD）和健康衰老相比。在项目2中，我们将使用4.0 Tesla磁铁探索三种主要FTLD综合征的成像特征和新的ALS患者队列。该项目将使用新的成像技术，包括基于张量的形态计量学，灌注和扩散张量成像。在项目第三项目中，我们将使用从基本情绪研究中得出的方法来评估与AD相比的所有三个FTLD亚型中的情绪功能（反应性，调节，知识）。将确定患者与看护者之间的二元组相互作用，低级情绪处理以及对这些基本情绪刺激的高阶反应。项目4将使用通过临床核心，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来探索彼此之间的更好分离FTLD亚型，并从AD中，早期诊断，并更好地预测FTLD相关的患者患有FTLD-泛素病理患者的TAU病理学。一个新的项目5使用新颖和创新的认知和社会探针探索了FTLD中脑行为的关系。使用项目2中的4.0 Tesla扫描，背侧区域的变化与运动反应的认知控制的特定方面与情绪的调节，腹侧和中间前额叶区域的变化与激活情绪系统的关系以监测监测的情绪系统之间的关系将探索行为以及前颞叶与言语和非语言刺激的理解之间的关系。项目1的重点是找到与FTLD相关的新基因的遗传学核心，该遗传学核心不仅将进行载脂蛋白E，TAU和Presenilin 1的常规研究，而且还将探索与Tau相关的和额叶相关基因的mRNA表达。通过Clincial Core Nove Nove评估107 AD，131 FTD，67 SD，56 PNFA，43 CBD，30 PSP，59 ALS和89个控制措施将在10年级完成。神经病理学将在37 AD，64 FTD，25，25，25 SD，23 PNFA，23 CBD，23个PSP和27名ALS患者。该PPG是了解有史以来FTLD的临床特征的最大努力之一。首席研究人员：米勒博士在不列颠哥伦比亚大学接受了医学和神经系统培训。然后，他在加利福尼亚大学洛杉矶分校（UCLA）完成了行为神经病学博士后奖学金。他对额叶叶变性（FTLD）的兴趣始于他在加州大学洛杉矶分校（UCLA），这仍然是他的主要兴趣。世界上很少有研究小组专注于FTLD，也许是因为很难调和其异质临床和神经病理学表现。米勒博士已经组建了一个跨学科的研究人员团队，该团队在与FTLD有关的临床，行为，神经病理学，成像和遗传问题方面具有专业知识。显然，它是世界上在这一领域工作的主要团体之一。 FTLD是一个研究的研究，尤其是具有挑战性的调查领域。总体而言，该计划项目代表了世界上试图理解和治疗该患者人群的最佳群体之一。综述组件核心A-临床和行政；博士Bruce L. Miller的描述（由申请人提供）：临床和行政核心为整个PPG提供了必不可少的操作功能。该核心将招募患有额颞痴呆（FTD），语义痴呆（SD），进行性非浮力失语（PNFA），渐进性上核麻痹（PSP），皮质巴萨（PSP），皮质性巴萨变性（CBD），肌萎缩性后期孢子虫（Als），艾尔兹（Als），阿尔兹（Alzheimers）（Alzheimerses）（Alzheimerses（Als））的核心。 AD）和正常对照对象。每个受试者都将获得全面的评估，以衡量广泛的神经心理学，功能，神经行为和社会人格变量。此外，每年将遵循受试者，以收集纵向数据并保持高度入学术中的尸检计划。该核心的行政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，确保对PPG资源的最佳利用和监测以及确保所有PPG实践的科学和伦理完整性。一旦招募到临床和行政核心，就会将受试者转介给项目2（成像； Weiner博士），3（情感； Levenson博士），4（临床诊断； Miller博士）和5（Brain-Behavior; Brain-Behavior;罗森博士）。此外，血液样本将被发送到遗传学核心（Geschwind博士），尸检组织将被发送到病理核心（Trojanowski和Lee博士）。临床和行政核心还将与数据管理和生物统计学核心（FOX博士）进行广泛互动，以进行数据管理，数据质量和数据分析功能。