Genetic studies have demonstrated four genetic loci for Alzheimer's disease; the amyloid precursor protein (APP) gene, presenilin 1 (PS1) on chromosome 14, presenilin 2 (PS2) on chromosome 1, and the apolipoprotein E (ApoE), locus/region of chromosome 19. While the first 3 are rare causes of Alzheimer's disease (AD), ApoE is a significant risk factor for late-onset AD. In addition to these known loci, other AD genes remain to be identified. Candidates for additional AD loci include the HLA A gene on chromosome 6, and the alpha-2-macroglobulin and lipoprotein receptor protein genes on chromosome 12. Others remain to be mapped. ApoE genotype has become a covariate for many studies of AD, including epidemiologic, genetic, clinical, and neuropathologic studies. In many of these efforts, the ApoE genotype is being used to attempt to correlate phenotypic features with genetic subtypes. Other studies are using ApoE genotypes to attempt to identify the mechanism by which the ApoE epsilon4 allele serves as a risk factor for AD, and the mechanism by which the epsilon2 allele may be protective. The Molecular Genetic Analysis Core (Core G) will provide services to projects in the University of Washington Alzheimer's Disease Research Center (OW-ADRC), other AD and related projects at the University of Washington, the University of Southern California ADRC, and other researchers at the University of Southern California.. The following services will be provided: 1) DNA will be prepared and banked from AD patients and appropriate controls from a variety of studies. When possible, serum and plasma will also be banked. Each individual study will supply blood samples for preparation of DNA plasma and serum. 2) All patients and controls will be genotyped for the ApoE polymorphisms. 3) A new ApoE genotyping method will be developed which will be based on real-time quantitative PCR methods The assay will be easily automated for high-throughput genotyping. 4) The core will provide the capacity to genotype new genetic markers for AD and other closely related disorders as these markers become available. 5) The core will screen early-onset familial subjects for APP, PS1 and PS2 mutations.
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