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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(More)
Neurotoxic amyloid beta peptide (Abeta) accumulates in the brains of individuals with Alzheimer disease (AD). The APOE4 allele is a major risk factor for sporadic AD and has been associated with increased brain parenchymal and vascular amyloid burden. How apoE isoforms influence Abeta accumulation in the brain has, however, remained unclear. Here, we have(More)
(LDLR) family, is a multiligand receptor whose physiological functions are carried out by endocytosis of li-gands and activation of multiple signal transduction * transmembrane glycoprotein, is cleaved in trans-Golgi network by furin to generate 515 kDa ␣ subunit and 2001). The exact pathogenic mechanism(s) by which LRP contributes to neurotoxic A␤(More)
LRP (low-density lipoprotein receptor-related protein) is linked to Alzheimer's disease (AD). Here, we report amyloid beta-peptide Abeta40 binds to immobilized LRP clusters II and IV with high affinity (Kd = 0.6-1.2 nM) compared to Abeta42 and mutant Abeta, and LRP-mediated Abeta brain capillary binding, endocytosis, and transcytosis across the mouse(More)
The role of blood-brain barrier (BBB) transport in clearance of amyloid beta-peptide (Abeta) by Abeta immunotherapy is not fully understood. To address this issue, we studied the effects of peripherally and centrally administered Abeta-specific IgG on BBB influx of circulating Abeta and efflux of brain-derived Abeta in APPsw(+/-) mice, a model that develops(More)
Rashid Deane,1* Abhay Sagare,1* Katie Hamm,1 Margaret Parisi,1 Barbra LaRue,1 Huang Guo,1 Zhenhua Wu,1 David M. Holtzman,2 and Berislav V. Zlokovic1 1Frank P. Smith Laboratories for Neuroscience and Neurosurgical Research, Department of Neurosurgery and Division of Neurovascular Biology, Arthur Kornberg Medical Research Building, University of Rochester(More)
Colonic crypt cells possess basolateral Ca(2+)-regulated K+ channels which support Cl- secretion by providing the necessary driving force. The pharmacological characteristics of these channels were examined in Ussing chamber experiments of rat and rabbit colon mucosa by the use of blockers. The chromanol 293B, a blocker of KVLQT1 channels, and clotrimazole(More)
Experimental data suggest that multidrug resistance in cancer may be overcome by using an increased dose of anticancer agent(s) in combination with a resistance-modifying agent (RMA). We studied the pharmacokinetics and metabolism of both epirubicin (EPI) and verapamil (VPL) to explore the possible pharmacokinetic interactions between these two drugs. Ten(More)