FRONTOTEMPORAL DEMENTIA GENES, IMAGES, & EMOTIONS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本项目旨在确定额颞叶变性（FTLD）的遗传、影像学、情感和诊断特征。在项目1中，我们将定位克隆常染色体显性遗传额颞叶痴呆-肌萎缩性侧索硬化症（FTLD-ALS）的15号染色体上的一个位点；确定导致散发性FTLD和进行性核上性麻痹（PSP）易感性的tau连锁序列变化；绘制FTLD的易感性位点，这不是由于高渗透常染色体显性位点；识别和研究症状前个体和易感突变。在项目2中，我们将定义FTLD、阿尔茨海默病（AD）、PSP和对照组的结构、光谱和灌注变化。在项目3中，我们将使用行为研究的方法来评估FTLD、AD和正常对照组在情绪反应、知识调节和人格方面的差异和变化；评估FTLD家庭中与tau突变相关的情绪和人格变化；并通过研究与配偶的二元互动来评估FTLD、AD和对照组的行为。在项目4中，我们将通过前瞻性设计确定区分FTLD和AD的临床和定量方法的敏感性和特异性；测定与AD和健康对照相比，FTLD患者基底神经节和运动神经元功能的纵向变化；研究PSP的认知和行为特征。

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 represents an attempt to determine the genetic, imaging, emotional and diagnostic features of frontotemporal 1obar degeneration (FTLD). In project 1 we will positionally clone a locus on chromosome 15 for autosomal dominantly inherited frontotemporal lobar dementia-amyotrophic lateral sclerosis (FTLD-ALS); identify tau-linked sequence changes responsible for susceptibility to sporadic FTLD and progressive supranuclear palsy (PSP); map a susceptibility locus for FTLD that is not due to highly penetrant autosomal dominant loci; and identify and study pre-symptomatic individual and susceptibility mutations. In project 2 we will define the structural, spectroscopic and perfusion changes in FTLD, Alzheimer s disease (AD), PSP and controls. In project 3 we will use methods from behavioral research to evaluate differences and changes in emotional reactivity, regulation of knowledge, and personality in FTLD, AD, and normal controls; evaluate emotional and personality chang es associated with tau mutations in families with FTLD; and evaluate behavior in FTLD, AD, and controls by studying dyadic interaction with spouses. In project 4 we will determine with a prospective design the sensitivity and specificity of clinical and quantitative methods for differentiating FTLD and AD; determine the longitudinal changes in basal ganglia and motor neuron function in FTLD compared to AD and healthy controls; and study the cognitive and behavioral features of PSP.