To better understand amyloid-b (Ab) metabolism in vivo, we assessed the concentration of Ab in the CSF and plasma of APP V717F (PDAPP) transgenic mice, a model that develops age-dependent Alzheimer's disease (AD)-like pathology. In 3-month-old mice, prior to the development of Ab deposition in the brain, there was a highly significant correlation between Ab levels in CSF and plasma. In 9-month-old-mice, an age at which some but not all mice have developed Ab deposition, there was also a significant correlation between CSF and plasma Ab; however, the correlation was not as strong as that present in young mice. In further exploring CSF and plasma Ab levels in 9-month-old mice, levels of CSF Ab were found to correlate highly with Ab burden. Analysis of the CSF : plasma Ab ratio revealed a selective two-fold increase in plaque versus non-plaque bearing mice, strongly suggesting a plaquemediated sequestration of soluble Ab in brain. Interestingly, in 9-month-old mice, a significant correlation between CNS and plasma Ab was limited to mice lacking Ab deposition. These findings suggest that there is a dynamic equilibrium between CNS and plasma Ab, and that plaques create a new equilibrium because soluble CNS Ab not only enters the plasma but also deposits onto amyloid plaques in the CNS.