Genetic studies have demonstrated three genetic loci for Alzheimer's disease; the amyloid precursor protein (APP) gene, a chromosome 14 locus, and the apolipoprotein E (ApoE) locus/region of chromosome 19. While the first 2 are probably relatively rare causes of Alzheimer's disease (AD), ApoE is a significant risk factor for AD in late-onset AD. In addition to these known loci, other AD genes remain to be identified. One may be at the HLA A locus. Others remain to be mapped. ApoE genotype has become a covariable 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 will provide services to projects in the University of Washington Alzheimer's Disease Research Center (UW-ADRC), the University of Kansas Alzheimer's Disease Research Center, the Southern California Alzheimer's Disease Research Center, and to funded projects outside of these Alzheimer's Disease Research Centers. 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 polymorphism consisting of the epsilon2/epsilon3/epsilon4 haplotype system. 3) A new ApoE genotyping method will be developed which will be based on the oligo- ligation assay (OLA) methodology. 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 (e.g., the chromosome 14 locus and other LOAD loci). One potential marker is the HLA-A locus. Other early onset and late-onset markers are expected to be developed as new AD loci are identified. Also, as non-DNA markers in serum or plasma are developed, this Core will assay for these new markers.
Showing the most recent 10 out of 753 publications
