The performance of innovative research on Alzheimer and dementia and non-AD dementias in the context of brain aging increasinglyrequires synergisticinteractionsbetweenclinical branches of agiven study, pathologicalinformationand modern and sophisticatedgenetic analyses. Furthermore,a critical step in progress towards understandingthe pathophysiology (and thus ultimately treatment) of different forms of dementia is assessing how different genotypes contribute to variability in disease phenotype. This type of correlation is a preamble to the equally importantgoal of understandinggene-environment interactions. The UCLA Core for The Genetic Analysis of FTLD is an integrated, state-of-the art laboratory that studies the Genetics and Molecular Biology of Frontotemporal Dementia and related dementias. The Core leverages the clinical strengths of the UCSF Center for Memory and Aging and Alzheimer's Disease Research Center (ADRC), as well as the UCSF investigators'longitudinal studies of dementia that provides clinical material for research projects. To further understand FTLD genetics and establish more specific genetic markers of the disease the work of the core sets several Specific Aims which include: 1) collection and banking of DMA on subjects with FTLD, AD and control subjects;2) genotyping for known genetic risk factors (e.g. ApoE, Tau, Prion protein and PS-1);3) exploratory investigation of RNA expression profiles for biomarker discovery and patient classification using microarray technology, and 4) development of interdisciplinary collaborations and research training. The fundamental purpose of this core is service, and the data obtained will be highly supportive and useful for other ongoing hypothesis driven projects in the PPG. The Genetic Core will also provide genetic screening and will perform genotyping studies of familial FTLD and AD. These core services build upon the laboratory's expertise derived from previous and ongoing, synergistic, genetic projects involving assessment of genetic risk factors and neurobehavioral phenotypes in FTLD, sequencing of genes related to tau to identify novel genetic risk factors for FTLD and AD, functional genomic based biomarker discovery and microarray based profiling of individuals for peripheral biomarkers using peripheral tissues and established cell lines. In this way, the core provides the necessary genetic foundation for the PPG by leveraging existing expertise and resources, thus delivering its services in the most efficient manner.
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