1. Clearance of amyloid-beta by circulating lipoprotein receptors.
- Author
-
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, and Zlokovic BV
- Subjects
- Alzheimer Disease physiopathology, Amyloid Precursor Protein Secretases genetics, Animals, Heterozygote, Humans, Low Density Lipoprotein Receptor-Related Protein-1 blood, Mice, Amyloid beta-Peptides metabolism, Brain metabolism, Capillaries physiology, Cerebrovascular Circulation physiology, Low Density Lipoprotein Receptor-Related Protein-1 physiology
- 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.
- Published
- 2007
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