Expression of receptors for native and chemically modified low‐density lipoproteins in brain microvessels

Abstract

Despite the importance of cholesterol metabolism in the central nervous system, only relatively few studies have dealt with the cerebral uptake and transport of lipids into the brain compartment. These functions are mediated by the endothelium of brain microvessels, which forms the anatomical basis of the blood-brain barrier. By a reverse transcriptase PCR study of messenger RNA expression we could show, in bovine brain microvessels, the presence of transcripts of native low-density lipoprotein receptor and of both type I and II scavenger receptors. Brain microvessels therefore appear to play an active role in the uptake of native and modified low-density lipoproteins.

Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1- 40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer.

“…This has been confirmed in the present BMEC model and the expression of gp330/megalin shown by immunocytochemistry with mouse monoclonal 1H12 anti-human anti-gp330 antibodies, kindly provided by R. McCluskey, Harvard University (data not shown; Stins et al, unpublished observations). Figure 3 E illustrates that unlabeled LDL (low density lipoproteins) at concentrations as high as 800 g/ml does not affect the uptake of 125 I-AcLDL (1 nM) exposed for 1 h to the apical side of the HBMEC monolayers, indicating that LDL receptor does not participate in uptake of AcLDL, as shown previously (39,40).…”

“…This scavenger receptor was selected for our studies in view of its identification in brain microvasculature (39). Surface binding was evaluated at 37ЊC using cells briefly exposed (Fig.…”

Increased locomotor activity in mice lacking the low-density lipoprotein receptor

“…Low but detectable levels of LDLR RNA are found in brain [15]. As judged by in situ hybridization, LDLR expression is widely distributed in brain [30] and likely found in neurons, astrocytes, and endothelial cells [9,10,15,22,25,30]. However, LDLR null mutant mice (LDLR-/-) show no obvious anatomic defects in brain and thus LDLR has been considered to be of lesser importance in brain development and function than other family members such as LRP, ApoER2, or VLDLR [13].…”

Nanoparticles for the Treatment ofAlzheimer's Disease: Theoretical Rationale, Present Status and Future Perspectives

“…These findings strongly indicate the involvement of ApoE and B in nanoparticle-mediated drug transport across the BBB and the surfactant on the particle surface may serve as an anchor for ApoE [171]. It is well known that ApoE plays a key role in the transport of LDLs into the brain, and the LDL receptor exists on the BBB [118,[173][174][175][176][177]. Also, lipoprotein particles containing ApoE and ApoA-I are found in human cerebrospinal fluid [178].…”