Peripheral amyloid-beta levels regulate amyloid-beta clearance from the central nervous system

J Alzheimers Dis. 2009;16(2):325-9. doi: 10.3233/JAD-2009-0964.


Amyloid-beta (Abeta) is cleared from the brain by both proteolytic digestion and transport across the blood-brain-barrier into the peripheral circulatory system. To investigate the role peripheral Abeta levels play in regulating Abeta brain clearance, we measured the clearance of [125I]-Abeta(1-40) injected into the brains of liver-ligated rats that allowed peripheral Abeta levels to be maintained at elevated levels for approximately one hour with/without a single peripheral bolus of unlabeled Abeta(1-40). We found that elevating peripheral Abetalevels significantly decreased [125I]-Abeta(1-40) brain clearance, thus supporting the hypothesis that peripheral Abeta levels regulate Abeta clearance from the central nervous system.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacokinetics*
  • Analysis of Variance
  • Animals
  • Area Under Curve
  • Biological Transport, Active / physiology
  • Brain / drug effects
  • Brain / metabolism*
  • Iodine Isotopes / pharmacokinetics
  • Male
  • Metabolic Clearance Rate / physiology
  • Peptide Fragments / metabolism*
  • Peptide Fragments / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Amyloid beta-Peptides
  • Iodine Isotopes
  • Peptide Fragments
  • amyloid beta-protein (1-40)