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PMID: 17694066 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Clearance of amyloid-beta by circulating lipoprotein receptors.

Nature medicine ·Vol. 13 ·No. 9 ·2007-09-00 ·Pages 1029-31

Sagare A, Deane R, Bell RD, Johnson B, Hamm K, Pendu R, Marky A, Lenting PJ, Wu Z, Zarcone T, Goate A, Mayo K, Perlmutter D, Coma M, Zhong Z, Zlokovic BV

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.

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,physiology Mice
Chemicals
Amyloid beta-Peptides Low Density Lipoprotein Receptor-Related Protein-1 Amyloid Precursor Protein Secretases
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Sagare Abhay
Frank P. Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA.
Deane Rashid
Bell Robert D
Johnson Bradley
Hamm Katie
Pendu Ronan
Marky Andrew
Lenting Peter J
Wu Zhenhua
Zarcone Troy
Goate Alison
Mayo Kevin
Perlmutter David
Coma Mireia
Zhong Zhihui
Zlokovic Berislav V
References (15)
15 references, click to expand
  1. Novel therapeutic approach for the treatment of Alzheimer's disease by peripheral administration of agents with an affinity to beta-amyloid.
    J Neurosci. 2003 Jan 1;23(1):29-33 PMID: 12514198
  2. The alpha -chains of C4b-binding protein mediate complex formation with low density lipoprotein receptor-related protein.
    J Biol Chem. 2002 Jan 25;277(4):2511-6 PMID: 11705989
  3. LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms.
    Neuron. 2004 Aug 5;43(3):333-44 PMID: 15294142
  4. Clearance of Alzheimer's Abeta peptide: the many roads to perdition.
    Neuron. 2004 Sep 2;43(5):605-8 PMID: 15339642
  5. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice.
    Science. 1996 Oct 4;274(5284):99-102 PMID: 8810256
  6. Soluble low density lipoprotein receptor-related protein (LRP) circulates in human plasma.
    J Biol Chem. 1997 Sep 19;272(38):23946-51 PMID: 9295345
  7. Human apolipoprotein E4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model.
    J Neurosci. 2005 Mar 16;25(11):2803-10 PMID: 15772340
  8. The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate.
    J Biol Chem. 2005 May 6;280(18):17777-85 PMID: 15749709
  9. LRP and Alzheimer's disease.
    Rev Neurosci. 2005;16(2):123-35 PMID: 15959937
  10. Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel walls.
    Am J Pathol. 2005 Aug;167(2):527-43 PMID: 16049337
  11. Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid beta-peptide by the liver.
    Pharm Res. 2006 Jul;23(7):1407-16 PMID: 16779710
  12. Binding site structure of one LRP-RAP complex: implications for a common ligand-receptor binding motif.
    J Mol Biol. 2006 Sep 29;362(4):700-16 PMID: 16938309
  13. Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system.
    J Cereb Blood Flow Metab. 2007 May;27(5):909-18 PMID: 17077814
  14. Clearance of Alzheimer's amyloid-ss(1-40) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier.
    J Clin Invest. 2000 Dec;106(12):1489-99 PMID: 11120756
  15. RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain.
    Nat Med. 2003 Jul;9(7):907-13 PMID: 12808450
Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1078-8956
DOI
10.1038/nm1635
Published
2007-09-00
Epub
2007-00-12
Pages
1029-31
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC2936449
Subset
IM
Grants
NIA NIH HHS · P50 AG05681 · United States
NINDS NIH HHS · R37 NS034467 · United States
NINDS NIH HHS · R37 NS34467 · United States
NIA NIH HHS · R37 AG023084 · United States
NIA NIH HHS · P50 AG005681 · United States
NINDS NIH HHS · R01 NS034467 · United States
NINDS NIH HHS · R01 NS034467-07 · United States
NIA NIH HHS · R37 AG023084-02 · United States
External Links
PubMed source DOI: 10.1038/nm1635 PMC Full Text View journal details
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