Clearance of amyloid-β by circulating lipoprotein receptors

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