Detecting presymptomatic disease in inherited frontotemporal dementia

检测遗传性额颞叶痴呆的症状前疾病

• 批准号: 8241501
• 负责人: SUZEE EURIE LEE
• 金额: $ 15.24万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8241501
• 关键词: Aging; Atrophic; Autopsy; Behavioral; Biological Markers; Biological Neural Networks; Brain; California; Cells; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Data; Deltastab; Dementia; Deterioration; Development Plans; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Family; Family member; Frontotemporal Dementia; Functional disorder; Future; Gene Mutation; Genes; Genetic; Goals; Grant; Image; Individual; Inherited; Investigation; Knowledge; Literature; Magnetic Resonance Imaging; Memory; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolism; Methods; Mind; Molecular Biology; Monitor; Mutation; Natural History; Nerve Degeneration; Network-based; Neurodegenerative Disorders; Neurologist; Observational Study; Onset of illness; Pathogenesis; Pathway Analysis; Patients; Primary Progressive Aphasia; Process; Program Research Project Grants; Progranulin; Recording of previous events; Research; Research Design; Research Infrastructure; Research Personnel; Rest; Risk; San Francisco; Semantics; Series; Staging; Symptoms; Techniques; Testing; Time; Training; Universities; base; career; career development; cohort; disease-causing mutation; experience; functional decline; gray matter; improved; insight; morphometry; mutation carrier; neuroimaging; neuropathology; normal aging; novel; patient oriented; pre-clinical; proband; programs; tau Proteins; white matter; white matter change

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Suzee Lee, a behavioral neurologist at the University of California, San Francisco (UCSF). Dr. Lee is establishing herself as a young investigator in patient-oriented clinical research of neurodegenerative disorders. This K23 award will provide Dr. Lee with the support necessary to accomplish the following goals: (1) to become an expert at patient-oriented clinical research in frontotemporal dementia (FTD); (2) to conduct clinical investigations of presymptomatic carriers of genes implicated in FTD; (3) to implement novel and advanced neuroimaging techniques in clinical studies; and (4) to develop an independent clinical research career. To achieve these goals, Dr. Lee has assembled a mentoring team comprised of two co-primary mentors. Dr. Bruce Miller, clinical director of the UCSF Memory and Aging Center (MAC), directs a program project grant on FTD (FTD-PPG) and a Hillblom Aging Network grant to study normal aging. Dr. William Seeley, director the UCSF MAC Autopsy Program and the Neuropathology Core, conducts neuroimaging studies on selective vulnerability in neurodegenerative diseases to explore early-stage disease pathogenesis. The mentoring team also includes two collaborators: Dr. Maria-Luisa Gorno-Tempini, a neurologist who focuses on neuroimaging in primary progressive aphasia and Dr. John Neuhaus, a statistician, who is an expert in study design and biostatistical analysis. Early diagnosis of front temporal dementia is notoriously challenging. Dr. Lee's research will focus on detecting vulnerable brain networks in presymptomatic carriers of FTD gene mutations (Aims 1 and 2). Dr. Lee will use the existing infrastructure and subject cohorts of the FTD-PPG and Hillblom Aging Network to study 50 unaffected family members of probands with FTD to determine the effect of FTD-related genes on alterations in large-scale structural and functional connectivity neural networks. This research will be the first step in a series of investigations that will aid the longitudinal characterization of the natural history of FTD from its earliest stages, paving the way for the field to establish disease monitoring strategies and time points for future treatments in gene mutation carriers. PUBLIC HEALTH RELEVANCE: Improved understanding of when and where in the brain neurodegeneration begins in presymptomatic carriers of front temporal dementia genes are critical to early diagnosis and disease-monitoring. Characterizing the history of front temporal dementia in this way will be crucial for the successful implementation of future treatments of this disease.

描述（由申请人提供）：这是加州大学旧金山分校 (UCSF) 行为神经学家 Suzee Lee 博士的 K23 奖项申请。李博士正在将自己打造成以患者为导向的神经退行性疾病临床研究的年轻研究者。该K23奖项将为李博士提供实现以下目标所需的支持：（1）成为额颞叶痴呆（FTD）以患者为导向的临床研究专家； （2）对FTD相关基因症状前携带者进行临床调查； (3) 在临床研究中应用新颖、先进的神经影像技术； (4)发展独立的临床研究事业。为了实现这些目标，李博士组建了一个由两名联合主要导师组成的导师团队。 Bruce Miller 博士是加州大学旧金山分校记忆与衰老中心 (MAC) 的临床主任，负责 FTD (FTD-PPG) 项目拨款和 Hillblom 老龄化网络拨款，以研究正常衰老。 William Seeley 博士是加州大学旧金山分校 MAC 尸检项目和神经病理学核心主任，他对神经退行性疾病的选择性脆弱性进行神经影像学研究，以探索早期疾病发病机制。指导团队还包括两名合作者：Maria-Luisa Gorno-Tempini 博士（专注于原发性进行性失语症的神经影像学）和统计学家 John Neuhaus 博士（研究设计和生物统计分析方面的专家）。 前颞叶痴呆的早期诊断非常具有挑战性。 Lee 博士的研究重点是检测 FTD 基因突变症状前携带者的脆弱大脑网络（目标 1 和 2）。 Lee 博士将利用 FTD-PPG 和 Hillblom Aging Network 的现有基础设施和受试者队列来研究 50 名未受影响的 FTD 先证者家庭成员，以确定 FTD 相关基因对大规模结构和功能连接神经网络改变的影响。这项研究将是一系列研究的第一步，这些研究将有助于从最早阶段纵向描述 FTD 自然史，为该领域建立疾病监测策略和基因突变携带者未来治疗的时间点铺平道路。 公共卫生相关性：更好地了解前颞叶痴呆基因的症状前携带者大脑神经变性何时何地开始，对于早期诊断和疾病监测至关重要。以这种方式描述前颞叶痴呆的病史对于成功实施该疾病的未来治疗至关重要。