During the last two decades many genes have been shown to cause autosomal dominant forms of early onset dementing illnesses. These rare disorders have provided enormous insight into the pathogenesis of more common variants of the same diseases. Several of the most promising new therapeutics are based on the Afi hypothesis, a hypothesis largely supported by the causative mechanisms of disease mutations in autosomal dominant families. As these putative therapeutics are tested in clinical trials there is a growing need to use the FAD kindreds both to understand the natural history of the earliest clinical and preclinical phases of the disease and to test the efficacy of the therapeutics in a setting, where if the Afi hypothesis is correct, they should have a dramatic effect on prognosis. The first step in this overarching goal is to bring together a network of centers to characterize a large series of FAD kindreds with known disease-causing mutations. The goal of the Genetics Core of the DIAN initiative is to provide genetic information and useful biological materials to the research community for the study of AD. We will collect blood samples for DMA extraction from all study participants (n=300). Since these individuals are part of FAD kindreds with known causative mutations we will screen each sample for the known mutation in that family and genotype all families for known disease modifying alleles such as APOE e4. Blood from each individual will be sent to NCRAD for transformation to develop lymphoblastoid cell lines that will provide the largest resource of cell lines from FAD kindreds with known disease-causing mutations anywhere in the world.
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