This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In MIRAGE III, the researchers are turning their attention to the growing body of evidence from pathological, epidemiological and genetic studies that risk factors for vascualar disease also enhance the risk of AD. However, since most epidemiological studies lack neuroimaging data, it is unclear whether the apparent association between vascular risk factors and AD is medicated via ischemic injury to the brain, acceleration of the primary Alzheimer's neurodegenerative process, or some other process. Some vascular risk factors are more prevalent in African American and Japanese American populations than in Caucasians. The researchers involved in vascular function and other indicators of cerebrovascular health including blood pressure and structural brain imaging (MRI), and susceptibility to AD in these ethnic groups. In order to carry out this project successfully, a sample of 1000 patients (500 Caucasians, 300 African Americans, 200 Japanese Americans) who meet NINCDS/ADRDA critera for probable or definite AD from 11 centers in the US, Canada and Germany will be collected from the probands and living siblings, spouses and children over the age of 50 years. DNA, plasma A beta isoforms and MRI of the brain will be evaluated in probands and siblings. The scientific aims of the are: 1. To examine recently discovered associations between the risk of AD and magnetic resonance imaging (MRI) variables, adjusting for APOE genotype and other risk factors. 2. To examine the association between single nucleotide polymorphisms (SNP's) in 100 genes posited to have a role in vascular function and AD in 1000 sibships using high throughput genotyping technology, and sibling pair linkage and family-based association methodologies. 3. To compare the relative contributions of these SNP's and other factors including blood pressure, treatment for hypertension, and plasma Abeta of disease and imaging otucomes in Caucasian, African American and Japanese American Sibships.
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