The main objective of this study was to determine whether elevated blood beta-amyloid (A beta) levels among the first-degree relatives of patients with Alzheimer's Disease (AD) are associated with vascular risk factors of AD. Serum A beta was measured in samples from 197 cognitively normal first-degree relatives of patients with AD-like dementia, Study participants were recruited as part of an ancillary study of the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT subpopulation). The ADAPT subpopulation was found to be similar in age, sex, and ethnicity to another cognitively normal cohort (n = 98). Using cross-sectional analyses, we examined the association of A beta with blood pressure, lipid levels, apolipoprotein E genotypes, and the use of prescribed medication to treat vascular risk factors in the ADAPT subpopulation. A beta(1-40) was positively associated with age, use of antihypertensives, and serum creatinine, and we observed a marginal negative interaction on A beta(1-40) associated with systolic blood pressure and use of antihypertensives. Serum A beta(1-42) was associated with statin use and a positive correlation of A beta(1-42) with HDL was observed among statin nonusers. These findings suggest that high A beta in the periphery among the family history-enriched cohorts may be due to enrichment of vascular risk factors and may reflect presymptomatic AD pathology. It remains to be determined whether the association of A beta with medications used for treating vascular risk factors indicates prevention of AD. Longitudinal evaluation of blood A beta in this cohort will provide a better understanding of the significance of this association in AD etiology. (C) 2009 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2008.00118