title: Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer's disease: the role, regulation and restoration of LRP1.
abstract: Amyloid beta (Aβ) homeostasis in the brain is governed by its production and clearance mechanisms. An imbalance in this homeostasis results in pathological accumulations of cerebral Aβ, a characteristic of Alzheimer's disease (AD). While Aβ may be cleared by several physiological mechanisms, a major route of Aβ clearance is the vascular-mediated removal of Aβ from the brain across the blood-brain barrier (BBB). Here, we discuss the role of the predominant Aβ clearance protein-low-density lipoprotein receptor-related protein 1 (LRP1)-in the efflux of Aβ from the brain. We also outline the multiple factors that influence the function of LRP1-mediated Aβ clearance, such as its expression, shedding, structural modification and transcriptional regulation by other genes. Finally, we summarize approaches aimed at restoring LRP1-mediated Aβ clearance from the brain.
authors.affiliation: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Nelson
authors.affiliation: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: Abhay P
authors.initials: AP
authors.lastname: Sagare
authors.affiliation: Department of Physiology and Biophysics, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California Los Angeles, CA, USA.
authors.forename: Berislav V
authors.initials: BV
authors.lastname: Zlokovic
keywords: Alzheimer’s disease (AD); PICALM; amyloid β clearance; blood-brain barrier; lipoprotein receptor-related protein 1 (LRP1)