Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

“…AD brain microvessels also show diminished expression of LRP1, a major Aβ clearance receptor at the BBB 19,20,156,190,191 (which change is also present in patients with hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D) 20 ). Diminished LRP1 expression leads to reduced Aβ clearance from the brain, promoting its accumulation in the brain 20,22,24 . Thus, LRP1 is a key target for enhancing transvascular Aβ clearance 192 .…”

Understanding the functions and relationships of the glymphatic system and meningeal lymphatics

“…Indeed, studies report transvascular clearance of Aβ primarily via LDL receptor-related protein 1 but also its removal by pericytes and myeloid cells (105)(106)(107)(108)(109)(110)(111). All these systems, including glymphatic and lymphatic drainage, must work in symbiosis to ensure the proper removal of protein.…”

Vascular and Metabolic Factors in Alzheimer’s Disease and Related Dementias: Introduction

“…Brain Aβ clearance is thought to rely on parenchymal and vascular mechanisms (Miners et al, 2014). In addition to parenchymal enzymes that degrade Aβ (neprilysin, insulin degrading enzyme, plasmin, and endothelin converting enzyme) (Miners et al, 2008), Aβ is removed (a) through perivascular pathways draining into the cervical lymphnodes (Tarasoff-Conway et al, 2015), and (b) by binding vascular transport receptors (LRP1, PICALM) and crossing the vascular wall to reach the circulation (Shibata et al, 2000; Storck et al, 2015; Zhao et al, 2015). A paravascular pathway involving astrocytic end-feet (glymphatic system), which has the potential to clear Aβ from the brain (Iliff et al, 2012), has been recently discovered and could play a role.…”