Role of the low-density lipoprotein receptor-related protein in beta-amyloid metabolism and Alzheimer disease

Arch Neurol. 2000 May;57(5):646-50. doi: 10.1001/archneur.57.5.646.


Deposition of beta-amyloid (A beta), a metabolite of approximately 4 kd of the amyloid precursor protein, is a critical pathological feature in Alzheimer disease. We postulate that deposition reflects an imbalance of A beta synthesis and clearance. Several pathways that impact A beta converge on a single receptor molecule, the low-density lipoprotein receptor-related protein (LRP). This multifunctional receptor is the major neuronal receptor both for apolipoprotein E (apoE, protein; APOE, gene) and for alpha2-macroglobulin (alpha2M, protein; A2M, gene), and it mediates clearance of apoE/A beta and alpha2M/A beta complexes. The LRP also interacts with the amyloid precursor protein itself. In this review, we highlight data that support a role for LRP in A beta metabolism and hypothesize that LRP therefore plays a critical role in Alzheimer disease.

Publication types

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

MeSH terms

  • Aged
  • Alleles
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / metabolism
  • Apolipoproteins E / metabolism
  • Binding, Competitive
  • Humans
  • Ligands
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Middle Aged
  • Polymorphism, Genetic
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, LDL / metabolism*


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Apolipoproteins E
  • Ligands
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Receptors, Immunologic
  • Receptors, LDL