FRONTOTEMPORAL DEMENTIA: GENES, IMAGES, AND EMOTIONS

描述（由申请人提供）：该计划项目代表了一个 试图确定遗传，成像，情感和诊断特征 额颞叶变性（FTLD）。在项目1中，我们将定位 在15号染色体上克隆一个常染色体显性遗传的位点 额颞叶痴呆-肌萎缩侧索硬化（FTLD-ALS）; 鉴定导致对以下疾病易感性的tau连锁序列变化 散发性FTLD和进行性核上性麻痹（PSP）;绘制易感性图 不是由于高外显常染色体显性基因座引起的FTLD基因座; 识别和研究症状前个体和易感性 突变。在项目2中，我们将定义结构，光谱和 FTLD、阿尔茨海默病（AD）、PSP和对照组的灌注变化。在 项目3我们将使用行为研究的方法来评估差异 以及情绪反应、知识调节和个性的变化 在FTLD、AD和正常对照中;评估情绪和人格变化 与FTLD家族中的tau突变相关;并评估 FTLD，AD和对照组通过研究与配偶的双向互动。在项目 4我们将采用前瞻性设计确定 鉴别FTLD和AD的临床和定量方法; 确定基底神经节和运动神经元功能的纵向变化 与AD和健康对照组相比，FTLD的认知和 PSP的行为特征

DESCRIPTION (provided by applicant): 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 changes 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.