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. Our attention is turned to the growing body of evidence from pathological, epidemiological and genetic studies that state that risk factors for vascular disease also enhance risk of AD in this study. However, since most epidemiological studies lack neuroimaging data, it is unclear whether the apparent association between vascular risk factors and AD is mediated via ischemic injury to the brain, acceleration of the primary Alzheimer neurodegenerative process, or some other process. Some vascular risk factors are more prevalent in African American and Japanese American populations than in Caucasians. We propose to build upon our earlier work by evaluating the association between APOE, genes involved in vascular function, and other indicators of cerebrovascular health, including blood pressure and structural brain imaging (MR1), and susceptibility to AD in these ethnic groups. In order to carry out this project successfully, we will ascertain a sample of 1000 patients (500 Caucasian, 300 African American, 200-Japanese American) who meet NINCDS/ADRDA criteria for probable or definite AD from 11 centers in the U.S., Canada and Germany. Many patients will be identified from our existing family registry. Family history, medical history, and epidemiological information will be obtained from AD probands and their first-degree relatives using standardized questionnaire instruments and established protocols. A cognitive screening test will be administered to and blood samples will be collected from the proband 's living sibs, spouses and children over the age of 50 years. DNA, plasma Ap isoforms and MRI of the brain will be evaluated in probands and sibs. The scientific aims of this project are: 1. To examine recently discovered associations between risk of AD and magnetic resonance imaging (MRl) variables, adjusting for APOE genotype and other known risk factors. 2. To examine the association between single nucleotide polymorphisms (SNPs) in lOO genes posited to have a role in vascular function and AD in 1000 siblings using high throughput genotyping technology, and sib-pair linkage and family-based association methodologies. 3. To compare the relative contributions of these SNPs and other factors including blood pressure, treatment for hypertension, and plasma A on disease and imaging outcomes in Caucasian, African American and Japanese American siblings. The targeted enrollment numbers include 100 proband and at least one sibling. Progress 2003-2004 This study is still in the recruitment phase. Twenty-five probands and with at least one sibling will be recruited per year for four years. Twenty-three families have been recruited this year with 15 cases completed inclusive of 60 participants. Thirty MRI's completed and 15 cases completed.
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