Clearance of amyloid-beta by circulating lipoprotein receptors.

Sagare, Abhay; Deane, Rashid; Bell, Robert D; Johnson, Bradley; Hamm, Katie; Pendu, Ronan; Marky, Andrew; Lenting, Peter J et al. · Nat Med · 2007

basic_science · Level V

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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.

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