Role of the low-density lipoprotein receptor-related protein in beta-amyloid metabolism and Alzheimer disease.
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.
Hyman
B T
BT
Alzheimer Disease Research Laboratory, Massachusetts General Hospital, Boston, USA. B_Hyman@helix.mgh.harvard.edu
Strickland
D
D
Rebeck
G W
GW
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism; D001667:Binding, Competitive; D006801:Humans; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D008024:Ligands; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL