FRONTOTEMPORAL DEMENTIA GENES, IMAGES, & EMOTIONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目代表了试图确定额颞叶变性（FTLD）的遗传，成像，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-肌萎缩侧索硬化症15号染色体上的一个位点（FTLD-ALS）;鉴定负责对散发性FTLD和进行性核上性麻痹（PSP）的易感性的tau连锁序列变化;绘制不是由于高度外显的常染色体显性基因座的FTLD的易感性基因座;并识别和研究症状前的个体和易感性突变。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和正常对照组中情绪反应，知识调节和个性的差异和变化;评估FTLD家族中与tau突变相关的情绪和个性变化;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，我们将采用前瞻性设计确定临床和定量方法区分FTLD和AD的敏感性和特异性;确定FTLD与AD和健康对照相比基底神经节和运动神经元功能的纵向变化;并研究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.