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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该计划项目赠款将确定额颞叶变性（FTLD）和相关疾病的成像，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）和健康老龄化形成对比。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患者的影像学特征。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，我们将使用来自基础情绪研究的方法来评估所有三种FTLD亚型与AD相比的情绪功能（反应性，调节性，知识）。将确定患者和护理人员之间的二元互动，低水平的情绪处理和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，以探索更好地将FTLD亚型彼此分离并与AD分离，早期诊断和更好地预测FTLD相关tau病理学患者与FTLD-泛素病理学患者。一个新的项目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的4.0特斯拉扫描，将探索背侧额叶区域的变化与运动反应的认知控制和情绪调节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测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。项目1的重点是寻找与FTLD相关的新基因，由遗传学核心取代，该核心不仅将进行载脂蛋白E，tau和早老素1的常规研究，而且还将探索tau相关和额叶相关基因的mRNA表达。通过临床核心新评估，107例AD、131例FTD、67例SD、56例PNFA、43例CBD、30例PSP、59例ALS和89例对照将在第10年完成。将在37例AD、64例FTD、25例SD、23例PNFA、23例CBD、23例PSP和27例ALS患者中完成神经病理学检查。该PPG代表了为了解FTLD临床特征所做的最大努力之一。主要医师：米勒博士在不列颠哥伦比亚省大学接受医学和神经病学培训。然后，他在洛杉矶的加州大学（UCLA）完成了行为神经学博士后研究。他对额颞叶变性（FTLD）的兴趣始于他在加州大学洛杉矶分校的时候，现在仍然是他的主要兴趣。世界上很少有研究小组关注FTLD，可能是因为它很难调和其异质性的临床和神经病理表现。米勒博士组建了一个跨学科的研究团队，他们在与FTLD相关的临床、行为、神经病理学、成像和遗传问题方面具有专业知识。它显然是世界上在这一领域工作的主要集团之一。FTLD是一个研究不足、重要且特别具有挑战性的调查领域。总的来说，该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。核心A组件审查-临床和给药; Dr.布鲁斯L.米勒描述（由申请人提供）：临床和管理核心为整个PPG提供基本操作功能。该核心研究将招募额颞叶痴呆（FTD）、语义性痴呆（SD）、进行性非流利性失语（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（ALS）、阿尔茨海默病（AD）患者和正常对照受试者。每名受试者将接受全面评估，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，将每年对受试者进行随访，以收集纵向数据，并在我们的尸检项目中保持高入组率。该核心的行政职能包括建立政策和程序的基础设施，保持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测，并确保所有PPG实践的科学和道德完整性。一旦招募到临床和管理核心，受试者将被转介到项目2（成像; Dr. Weiner）、项目3（情感; Dr. Levenson）、项目4（临床诊断; Dr.米勒）和项目5（大脑行为; Dr.罗森）。此外，血液样本将送至遗传学中心（Geschwind博士），尸检组织将送至病理学中心（Trojanowski和Lee博士）。临床和行政核心还将与数据管理和生物统计核心（Fox博士）就数据管理、数据质量和数据分析功能进行广泛互动。