The primary aim of this study is to determine the occurrence of genetic differences between incident, clinically diagnosed Alzheimer's Disease (DAT) cases and population-based control subjects. Duplication of the DNA sequence which codes for A4 amyloid on chromosome 21 will be evaluated for its sensitivity and specificity as a diagnostic marker for DAT when compared to the NINCDS/ADRDA diagnosis of Probable Alzheimer's Disease. Amyloid of this type is found at autopsy in the brains of DAT patients and also in elderly Down syndrome patients with dementia. The importance of environmental risk factors relative to genetic status will be evaluated to describe possible diagnostic subtypes or etiologic heterogeneity of DAT. Incident DAT cases will be obtained from the Alzheimer's Disease Patient Registry (ADPR) at Group Health Cooperative (GHC) in Seattle. Approximately 200 cases from the ADPR and 200 control subjects selected from the GHC rolls (frequency matched for age and sex) will participate in this study. Epidemiologic data, family history and demographics are to be obtained from case and case-proxy prior to diagnosis of DAT and stored in the ADPR database. Control and control proxy are screened to rule out cognitive impairment and then similar data are obtained. Controls are retested annually to assure that no change has occurred in their cognitive status. Both cases and control subjects will provide blood samples to be used in the laboratory analysis.
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