About 90% of the soluble amyloid beta (sA beta) that circulates in normal human plasma is associated with lipoprotein particles. In sporadic Alzheimer's disease patients, free sA beta42 but not sA beta40 is increased approximately 2.3-fold compared with age-matched controls, although a more marked elevation (approximately 8-fold for free sA beta40 and about 20-fold for sA beta42) is found in Down's syndrome patients. The data suggest that lipoprotein-sA beta dissociation may contribute to the influx of sA beta into the brain as a result of decreased plasma clearance.