title: Clearance of amyloid-beta by circulating lipoprotein receptors.
abstract: 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.
authors: Frank P. Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA.
authors: Abhay
authors: A
authors: Sagare
authors: Rashid
authors: R
authors: Deane
authors: Robert D
authors: RD
authors: Bell
authors: Bradley
authors: B
authors: Johnson
authors: Katie
authors: K
authors: Hamm
authors: Ronan
authors: R
authors: Pendu
authors: Andrew
authors: A
authors: Marky
authors: Peter J
authors: PJ
authors: Lenting
authors: Zhenhua
authors: Z
authors: Wu
authors: Troy
authors: T
authors: Zarcone
authors: Alison
authors: A
authors: Goate
authors: Kevin
authors: K
authors: Mayo
authors: David
authors: D
authors: Perlmutter
authors: Mireia
authors: M
authors: Coma
authors: Zhihui
authors: Z
authors: Zhong
authors: Berislav V
authors: BV
authors: Zlokovic
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002196:Capillaries / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000097:blood / Q000502:physiology*; D051379:Mice
chemical_list: D016229:Amyloid beta-Peptides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D053829:Amyloid Precursor Protein Secretases
references: J Neurosci. 2003 Jan 1;23(1):29-33
references: 12514198
references: J Biol Chem. 2002 Jan 25;277(4):2511-6
references: 11705989
references: Neuron. 2004 Aug 5;43(3):333-44
references: 15294142
references: Neuron. 2004 Sep 2;43(5):605-8
references: 15339642
references: Science. 1996 Oct 4;274(5284):99-102
references: 8810256
references: J Biol Chem. 1997 Sep 19;272(38):23946-51
references: 9295345
references: J Neurosci. 2005 Mar 16;25(11):2803-10
references: 15772340
references: J Biol Chem. 2005 May 6;280(18):17777-85
references: 15749709
references: Rev Neurosci. 2005;16(2):123-35
references: 15959937
references: Am J Pathol. 2005 Aug;167(2):527-43
references: 16049337
references: Pharm Res. 2006 Jul;23(7):1407-16
references: 16779710
references: J Mol Biol. 2006 Sep 29;362(4):700-16
references: 16938309
references: J Cereb Blood Flow Metab. 2007 May;27(5):909-18
references: 17077814
references: J Clin Invest. 2000 Dec;106(12):1489-99
references: 11120756
references: Nat Med. 2003 Jul;9(7):907-13
references: 12808450