Role of Vitamin D in Amyloid clearance via LRP-1 upregulation in Alzheimer's disease: A potential therapeutic target?

Amyloid beta (A beta) deposition is considered to be one of the primary reason to trigger Alzheimer's disease (AD). Literature clearly suggests decline in A beta clearance to be accountable for progression of late onset AD as compared to augmented A beta production. There may be several pathways for A beta clearance out of which one of the major pathway is the vascular-mediated removal of A beta from the brain across the blood brain barrier (BBB) via efflux pumps or receptors. Among A beta scavenger receptors, low density lipoprotein receptor related protein (LRP-1) has been most extensively studied. LRP-1, is highly expressed in neurons and located on abluminal side of the brain capillaries whose expression decreases in AD patients which give rise to increased cerebral A beta deposition. Recent evidences reveal that post 1,25-(OH)(2)D-3 treatment, LRP1 expression increases significantly for both in-vivo and in-vitro studies, since Vitamin D receptors (VDR) are broadly expressed in brain. Biological actions of Vitamin D are mediated via its nuclear hormone receptor vitamin D receptor (VDR) and is found to regulate many genes. Several lines of evidence suggest that VDR deficiency/inhibition can be a potential risk factor for AD and sufficient Vitamin D supplementation is beneficial to prevent AD onset/pathology or slow down the progression of disease. The present review establishes a strong correlation between Vitamin D and LRP-1 and their possible involvement in A beta clearance and thereby emerging as new therapeutic target. (C) 2017 Elsevier B.V. All rights reserved.