Clearance of amyloid-beta by circulating lipoprotein receptors

Nat Med. 2007 Sep;13(9):1029-31. doi: 10.1038/nm1635. Epub 2007 Aug 12.


Low-density lipoprotein receptor-related protein-1 (LRP) on brain capillaries clears amyloid beta-peptide (Abeta) from brain. Here, we show that soluble circulating LRP (sLRP) provides key endogenous peripheral 'sink' activity for Abeta in humans. Recombinant LRP cluster IV (LRP-IV) bound Abeta in plasma in mice and Alzheimer's disease-affected humans with compromised sLRP-mediated Abeta binding, and reduced Abeta-related pathology and dysfunction in a mouse model of Alzheimer disease, suggesting that LRP-IV can effectively replace native sLRP and clear Abeta.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / physiopathology
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism*
  • Capillaries / physiology*
  • Cerebrovascular Circulation / physiology*
  • Heterozygote
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / blood
  • Low Density Lipoprotein Receptor-Related Protein-1 / physiology*
  • Mice


  • Amyloid beta-Peptides
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Amyloid Precursor Protein Secretases