Clearance of amyloid-β by circulating lipoprotein receptors

Abhay Sagare, Rashid Deane, Robert D. Bell, Bradley Johnson, Katie Hamm, Ronan Pendu, Andrew Marky, Peter J. Lenting, Zhenhua Wu, Troy Zarcone, Alison Goate, Kevin Mayo, David Perlmutter, Mireia Coma, Zhihui Zhong, Berislav V. Zlokovic

Research output: Contribution to journalArticle

316 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)1029-1031
Number of pages3
JournalNature Medicine
Volume13
Issue number9
DOIs
StatePublished - Sep 2007

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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