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

doi:10.1038/nm1635

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 journal › Article › peer-review

379 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 language	English
Pages (from-to)	1029-1031
Number of pages	3
Journal	Nature Medicine
Volume	13
Issue number	9
DOIs	https://doi.org/10.1038/nm1635
State	Published - Sep 2007
Externally published	Yes

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title = "Clearance of amyloid-β by circulating lipoprotein receptors",

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.",

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

note = "Funding Information: This work was supported by US National Institutes of Health (NIH) grants R37 AG023084 and R37 NS34467 to B.V.Z. and Washington University St. Louis Alzheimer{\textquoteright}s Disease Research Center grant P50 AG05681.",

year = "2007",

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doi = "10.1038/nm1635",

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pages = "1029--1031",

journal = "Nature Medicine",

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T1 - Clearance of amyloid-β by circulating lipoprotein receptors

AU - Sagare, Abhay

AU - Deane, Rashid

AU - Bell, Robert D.

AU - Johnson, Bradley

AU - Hamm, Katie

AU - Pendu, Ronan

AU - Marky, Andrew

AU - Lenting, Peter J.

AU - Wu, Zhenhua

AU - Zarcone, Troy

AU - Goate, Alison

AU - Mayo, Kevin

AU - Perlmutter, David

AU - Coma, Mireia

AU - Zhong, Zhihui

AU - Zlokovic, Berislav V.

N1 - Funding Information: This work was supported by US National Institutes of Health (NIH) grants R37 AG023084 and R37 NS34467 to B.V.Z. and Washington University St. Louis Alzheimer’s Disease Research Center grant P50 AG05681.

PY - 2007/9

Y1 - 2007/9

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AB - 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.

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JO - Nature Medicine

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Clearance of amyloid-β by circulating lipoprotein receptors

Abstract

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