Cerebrovascular accumulation and increased blood-brain barrier permeability to circulating Alzheimer's amyloid beta peptide in aged squirrel monkey with cerebral amyloid angiopathy

J Neurochem. 1998 Jan;70(1):210-5. doi: 10.1046/j.1471-4159.1998.70010210.x.


Senescent squirrel monkey is a valuable model to study pathogenesis of cerebrovascular amyloid angiopathy (CAA). Cerebrovascular sequestration and blood-brain barrier (BBB) permeability to 121I-amyloid beta(1-40) synthetic peptide (sA beta(1-40)) were studied in adult versus aged squirrel monkey 1 h after a single intravenous injection. In aged monkey, the half-time of elimination of sA beta(1-40), t(1/2)e, was prolonged by 0.6 h, the systemic clearance, ClSS, was reduced from 1.8 to 1.1 ml/min/kg, and the mean residence time of intact peptide in the circulation was increased by 1 h (45%). In adult monkey, cerebrovascular sequestration of intact sA beta(1-40) was significant, and the BBB permeability was 18.6-fold higher than for inulin. In aged monkey, the sequestration of intact sA beta(1-40) by cortical and leptomeningeal microvessels and the BBB permeability were increased by 5.9, 1.8-, and 2.1-fold, respectively, in the presence of an unchanged barrier to inulin. In brain parenchyma of aged animals, 76.1% of circulating sA beta(1-40) remained intact versus 45.7% in adult. We conclude that multiple age-related systemic effects, i.e., reduced body elimination and systemic clearance of sA beta(1-40), and reduced peripheral metabolism, may act in concert with BBB mechanisms, i.e., increased transendothelial transport and microvascular accumulation of blood-borne sA beta(1-40), and reduced brain metabolism to enhance the development of CAA.

Publication types

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

MeSH terms

  • Aging / blood*
  • Alzheimer Disease / blood
  • Amyloid beta-Peptides / blood*
  • Amyloid beta-Peptides / pharmacokinetics
  • Animals
  • Blood-Brain Barrier / physiology*
  • Capillary Permeability / physiology*
  • Cerebral Amyloid Angiopathy / blood*
  • Cerebrovascular Circulation / physiology*
  • Chemical Precipitation
  • Peptide Fragments / blood
  • Peptide Fragments / pharmacokinetics
  • Saimiri
  • Tissue Distribution
  • Trichloroacetic Acid


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • Trichloroacetic Acid