Detecting presymptomatic disease in inherited frontotemporal dementia

项目摘要/摘要 这是为加州大学行为神经学家Suzee Lee博士申请K23奖项 加州，旧金山(加州大学旧金山分校)。李医生在《以病人为本》中确立了自己作为年轻研究员的地位 神经退行性疾病的临床研究。这项K23奖项将为李博士提供支持 要实现以下目标：(1)成为以患者为中心的临床研究专家 额颞痴呆(FTD)；(2)对症状前基因携带者进行临床调查 (3)在临床研究中应用新的和先进的神经成像技术；及(4) 发展独立的临床研究事业。为了实现这些目标，李博士组织了一项指导 由两位共同的小学导师组成的团队。加州大学旧金山分校记忆和衰老中心临床主任布鲁斯·米勒博士 中心(MAC)，指导FTD计划项目赠款(FTD-PPG)和Hillblom老龄网络赠款以进行研究 正常衰老。加州大学旧金山分校MAC尸检项目和神经病理核心主任威廉·西利博士， 对神经退行性疾病的选择性易损性进行神经成像研究，以探索早期 疾病发病机制。指导团队还包括两名合作者：玛丽亚-路易莎·戈尔诺-坦皮尼博士，一名 专注于原发性进行性失语的神经成像的神经学家和统计学家约翰·纽豪斯博士， 世卫组织是研究设计和生物统计分析方面的专家。 众所周知，额颞叶痴呆的早期诊断具有挑战性。李博士的研究将集中在 检测FTD基因突变的症状前携带者的脆弱脑网络(目标1和2)。李博士 将利用FTD-PPG和Hillblom老龄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确定FTD相关基因对改变的影响 在大规模的结构和功能连接神经网络中。这项研究将是 一系列调查，将有助于从其纵向描述FTD的自然历史 最早阶段，为实地建立疾病监测战略和未来时间点铺平道路 基因突变携带者的治疗。

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.