Clearance of amyloid-beta by circulating lipoprotein receptors.
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.
Sagare
Abhay
A
Frank P. Smith Laboratory for Neuroscience and Neurosurgical Research, Department of Neurosurgery, University of Rochester Medical School, Rochester, New York 14642, USA.
Deane
Rashid
R
Bell
Robert D
RD
Johnson
Bradley
B
Hamm
Katie
K
Pendu
Ronan
R
Marky
Andrew
A
Lenting
Peter J
PJ
Wu
Zhenhua
Z
Zarcone
Troy
T
Goate
Alison
A
Mayo
Kevin
K
Perlmutter
David
D
Coma
Mireia
M
Zhong
Zhihui
Z
Zlokovic
Berislav V
BV
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
D016229:Amyloid beta-Peptides; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D053829:Amyloid Precursor Protein Secretases
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