FRONTOTEMPORAL DEMENTIA GENES, IMAGES, & EMOTIONS

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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.