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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)
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)
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)
OBJECTIVE To determine the role of patched receptor (Ptc)-1 in mediating pulsatile flow-induced changes in vascular smooth muscle cell growth and vascular remodeling. APPROACH AND RESULTS In vitro, human coronary arterial smooth muscle cells were exposed to normal or pathological low pulsatile flow conditions for 24 hours using a perfused transcapillary(More)
OBJECTIVES To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling. METHODS AND RESULTS Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser(More)
Kimberly Patterson for their assistance with the experiment described in this chapter. " Theory of mind " refers to the tendency to construe people in terms of their mental states and traits (Premack & Woodruff, 1978). If we see someone grimace, we might infer that they are disappointed; if we see a man running to a bus, we probably infer that he is trying(More)
In 2011, a severe outbreak of hemolytic-uremic syndrome was caused by an unusual, highly virulent enterohemorrhagic E. coli (EHEC) O104:H4 strain, which possessed EHEC virulence traits in the genetic background of human-adapted enteroaggregative E. coli. To determine magnitude of fecal shedding and site of colonization of EHEC O104:H4 in a livestock host,(More)