Detecting presymptomatic disease in inherited frontotemporal dementia

检测遗传性额颞叶痴呆的症状前疾病

基本信息

批准号：
8516933
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
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8516933
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

项目摘要

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.

项目摘要/摘要这是为Suzee Lee博士颁发的K23奖，加利福尼亚，旧金山（UCSF）。李博士正在以患者为导向的年轻调查员建立自己神经退行性疾病的临床研究。该K23奖将为Lee博士提供支持实现以下目标所必需的：（1）成为以患者为导向的临床研究专家额颞痴呆（FTD）; （2）进行基因的预症状载体的临床研究与FTD有关；（3）在临床研究中实施新颖和先进的神经影像学技术；（4）到发展独立的临床研究职业。为了实现这些目标，李博士聚集了指导团队由两位联合主导者组成。 UCSF记忆与衰老临床主任Bruce Miller博士中心（Mac），指导FTD（FTD-PPG）和Hillblom老化网络赠款的计划项目赠款正常衰老。 UCSF MAC尸检计划和神经病理学核心主任William Seeley博士，对神经退行性疾病中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理。指导团队还包括两个合作者：Maria-Luisa Gorno-Tempini博士，专注于主要进行性渐进式失语症的神经影像学家和统计学家约翰·诺伊豪斯（John Neuhaus）博士谁是研究设计和生物统计分析的专家。众所周知，额颞痴呆的早期诊断是具有挑战性的。李博士的研究将重点放在检测FTD基因突变的预症状载体中脆弱的大脑网络（目标1和2）。李博士将使用FTD-PPG和Hillblom衰老网络的现有基础设施和主题队列研究50 不受影响的家庭成员具有FTD，以确定与FTD相关基因对改变的影响在大规模的结构和功能连通性神经网络中。这项研究将是一系列调查将有助于从其自然历史上纵向表征FTD的纵向表征最早的阶段，为该领域建立疾病监测策略和未来时间点铺平了道路基因突变载体的治疗。