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: 8334081
• 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/8334081
• 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; abstracting; 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

Project Summary/Abstract 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 frontotemporal 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.

项目总结/摘要 这是一份K23奖的申请书，申请人是苏茜·李博士，她是纽约大学的行为神经学家。 加州，旧金山弗朗西斯科（加州大学旧金山分校）。李博士正在建立自己作为一个年轻的研究人员在以病人为导向 神经退行性疾病的临床研究。这个K23奖将为李博士提供支持， 必须完成以下目标：（1）成为以患者为导向的临床研究专家， 额颞叶痴呆（FTD）;（2）进行症状前基因携带者的临床研究 涉及FTD;（3）在临床研究中实施新型和先进的神经成像技术;（4） 发展独立的临床研究事业。为了实现这些目标，李博士组建了一个指导小组， 团队由两名共同的主要导师组成。布鲁斯米勒博士，加州大学旧金山分校记忆和衰老临床主任 中心（MAC），指导FTD（FTD-PPG）的计划项目赠款和Hillblom老龄化网络赠款研究 正常老化。威廉塞利博士，加州大学旧金山分校MAC尸检项目和神经病理学核心主任， 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 发病机理指导小组还包括两名合作者： 专注于原发性进行性失语症神经影像学的神经学家和统计学家John Neuhaus博士， 他是研究设计和生物统计分析方面的专家。 额颞叶痴呆的早期诊断是众所周知的挑战。李博士的研究将集中在 检测FTD基因突变前驱携带者的脆弱脑网络（目的1和2）。李博士 将使用FTD-PPG和Hillblom老龄化网络的现有基础设施和受试者队列来研究50 FTD先证者未受影响的家庭成员，以确定FTD相关基因对改变的影响 大规模结构和功能连接神经网络。这项研究将是第一步， 一系列的调查，这将有助于纵向表征FTD的自然历史，从其 为实地确定疾病监测战略和今后的时间点铺平道路 基因突变携带者的治疗。