Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer's disease: the role, regulation and restoration of LRP1.

ABSTRACT: Amyloid beta (A?) homeostasis in the brain is governed by its production and clearance mechanisms. An imbalance in this homeostasis results in pathological accumulations of cerebral A?, a characteristic of Alzheimer's disease (AD). While A? may be cleared by several physiological mechanisms, a major route of A? clearance is the vascular-mediated removal of A? from the brain across the blood-brain barrier (BBB). Here, we discuss the role of the predominant A? clearance protein-low-density lipoprotein receptor-related protein 1 (LRP1)-in the efflux of A? from the brain. We also outline the multiple factors that influence the function of LRP1-mediated A? clearance, such as its expression, shedding, structural modification and transcriptional regulation by other genes. Finally, we summarize approaches aimed at restoring LRP1-mediated A? clearance from the brain.

SUBMITTER: Ramanathan A 

PROVIDER: S-EPMC4502358 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature