Amyloid efflux transporter expression at the blood-brain barrier declines in normal aging

J Neuropathol Exp Neurol. 2010 Oct;69(10):1034-43. doi: 10.1097/NEN.0b013e3181f46e25.


Reduced clearance of amyloid β peptides (Aβ) across the blood-brain barrier contributes to amyloid accumulation in Alzheimer disease. Amyloid β efflux transport is via the endothelial low-density lipoprotein receptor-related protein 1 (LRP-1) and P-glycoprotein (P-gp), whereas Aβ influx transport is via the receptor for advanced glycation end products. Because age is the major risk factor for developing Alzheimer disease, we measured LRP-1 and P-gp expression and associated transporter expression with Aβ accumulation in aging rats. Quantitative LRP-1 and P-gp microvessel expression was measured by immunohistochemistry (IHC); LRP-1 and P-gp expression were assessed in microvessel isolates by Western blotting. There was an age-dependent loss of capillary LRP-1 across all ages (3-36 months) by IHC (linear trend p = 0.0004) and between 3 and 20 months by Western blotting (linear trend p < 0.0001). There was a late (30-36 months) P-gp expression loss by IHC (p < 0.05) and Western blotting (p = 0.0112). Loss of LRP-1 correlated with Aβ42 accumulation (p = 0.0121) and very nearly with Aβ40 (p = 0.0599) across all ages. Expression of LRP-1 correlated negatively with the expression of receptor for advanced glycation end products (p < 0.0004). These data indicate that alterations in LRP-1 and P-gp expression seem to contribute progressively to Aβ accumulation in aging.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Age Factors
  • Aging / pathology*
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blood-Aqueous Barrier / physiology*
  • Gene Expression Regulation / physiology*
  • Linear Models
  • Male
  • Membrane Transport Proteins / metabolism
  • Microvessels / metabolism
  • Peptide Fragments / metabolism
  • Rats
  • Rats, Inbred F344
  • Receptor for Advanced Glycation End Products
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Amyloid
  • Amyloid beta-Peptides
  • Membrane Transport Proteins
  • Peptide Fragments
  • Receptor for Advanced Glycation End Products
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • peptidoglycan receptor