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

Ronald B. DeMattos, Kelly R. Bales, Maia Parsadanian, Mark A. O'Dell, Eric M. Foss, Steven M. Paul, David M. Holtzman

Research output: Contribution to journalArticle

209 Scopus citations

Abstract

To better understand amyloid-β (Aβ) metabolism in vivo, we assessed the concentration of Aβ in the CSF and plasma of APPV717F (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 Aβ deposition in the brain, there was a highly significant correlation between Aβ levels in CSF and plasma. In 9-month-old-mice, an age at which some but not all mice have developed Aβ deposition, there was also a significant correlation between CSF and plasma Aβ; however, the correlation was not as strong as that present in young mice. In further exploring CSF and plasma Aβ levels in 9-month-old mice, levels of CSF Aβ were found to correlate highly with Aβ burden. Analysis of the CSF: plasma Aβ ratio revealed a selective two-fold increase in plaque versus non-plaque bearing mice, strongly suggesting a plaque-mediated sequestration of soluble Aβ in brain. Interestingly, in 9-month-old mice, a significant correlation between CNS and plasma Aβ was limited to mice lacking Aβ deposition. These findings suggest that there is a dynamic equilibrium between CNS and plasma Aβ, and that plaques create a new equilibrium because soluble CNS Aβ not only enters the plasma but also deposits onto amyloid plaques in the CNS.

Original languageEnglish
Pages (from-to)229-236
Number of pages8
JournalJournal of Neurochemistry
Volume81
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Alzheimer
  • Amyloid precursor protein (APP)
  • Cerebrospinal fluid
  • Plaque
  • Transgenic
  • β-amyloid

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