Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium in a mouse model of Alzheimer's disease

J Neurochem. 2002 Apr;81(2):229-36. doi: 10.1046/j.1471-4159.2002.00889.x.


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

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Animals
  • Cerebrospinal Fluid / chemistry
  • Cisterna Magna / physiology
  • Cisterna Magna / surgery
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gyrus Cinguli / chemistry
  • Gyrus Cinguli / pathology
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Microsurgery / methods
  • Neurosurgical Procedures / methods
  • Plaque, Amyloid / metabolism*
  • Sex Factors


  • Amyloid beta-Peptides