The putative blood-brain barrier transporter for the β-amyloid binding protein apolipoprotein j is saturated at physiological concentrations

Shayo, Marcos; McLay, Robert N.; Kastin, Abba J.; Banks, William A.

doi:10.1016/s0024-3205(96)00685-6

Cited by 64 publications

(40 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings further suggest that if the levels of Aβ in brain extracellular space exceed the transport capacity of the clearance mechanism across the BBB, or if the vascular transport of the peptide were impaired, for example by downregulation of LRP-1, this would result in accumulation of Aβ in the brain, and possibly formation of amyloid plaques. Previous studies from our laboratory and others have demonstrated a major role of the BBB in determining the concentrations of Aβ in the CNS by regulating transport of circulating Aβ (33,39,(49)(50)(51)(62)(63)(64)(65)(66). This study extends this hypothesis by showing that vascular transport out of the brain across the BBB may represent a major physiological mechanism that prevents accumulation of Aβ and amyloid deposition in the brain.…”

Section: Discussionsupporting

confidence: 77%

“…Under our experimental con- ditions, the levels of radiolabeled Aβ in the circulation were two to three orders of magnitude lower than the brain levels. This makes re-entry of radiolabeled Aβ into the brain very unlikely, because the blood-to-brain transport of Aβ normally operates down the concentration gradient (39,(62)(63)(64)(65). In addition, the apoJ system that transports blood-borne Aβ into the brain is saturated under the physiological conditions (64) that may facilitate the efflux of Aβ from the brain.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier

Shibata

Yamada²,

Kumar³

et al. 2000

J. Clin. Invest.

1,261

1,226

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier

Shibata

Yamada²,

Kumar³

et al. 2000

J. Clin. Invest.

1,261

1,226

View full text Add to dashboard Cite

“…The thorax was opened, the heart was exposed, both jugulars were severed, and the descending thoracic aorta was clamped. A 26-gauge butterfly needle was inserted into the left ventricle of the heart, and the buffer of Zlokovic et al (23) containing I-Lep [2(10) 6 cpm/ml] was infused at a rate of 2 ml/min for 5 min (24). The exact counts per minute infused was determined on a 10-l aliquot of perfusion fluid.…”

Section: Methodsmentioning

confidence: 99%

Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier

et al. 2004

Self Cite

View full text Add to dashboard Cite

Obesity is associated with leptin resistance as evidenced by hyperleptinemia. Resistance arises from impaired leptin transport across the blood-brain barrier (BBB), defects in leptin receptor signaling, and blockades in downstream neuronal circuitries. The mediator of this resistance is unknown. Here, we show that milk, for which fats are 98% triglycerides, immediately inhibited leptin transport as assessed with in vivo, in vitro, and in situ models of the BBB. Fat-free milk and intralipid, a source of vegetable triglycerides, were without effect. Both starvation and diet-induced obesity elevated triglycerides and decreased the transport of leptin across the BBB, whereas short-term fasting decreased triglycerides and increased transport. Three of four triglycerides tested intravenously inhibited transport of leptin across the BBB, but their free fatty acid constituents were without effect. Treatment with gemfibrozil, a drug that specifically reduces triglyceride levels, reversed both hypertriglyceridemia and impaired leptin transport. We conclude that triglycerides are an important cause of leptin resistance as mediated by impaired transport across the BBB and suggest that triglyceride-mediated leptin resistance may have evolved as an anti-anorectic mechanism during starvation. Decreasing triglycerides may potentiate the anorectic effect of leptin by enhancing leptin transport across the BBB. Diabetes 53

show abstract

“…A 26-gauge butterfly needle was inserted into the left ventricle of the heart and the perfusate, containing 131 I-P-GUS or 131 I-NP-GUS with 125 I-albumin, was infused at a rate of 2 ml͞min for 1-10 min. This rate of perfusion quickly fills the vascular space in the brain without disrupting the BBB (20). After perfusion, the brain was removed and weighed.…”

Section: Transcardiac Brain Perfusion (19)mentioning

confidence: 99%

Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier

Urayama

Grubb

Sly

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

148

138

View full text Add to dashboard Cite

Mucopolysaccharidosis type VII is a lysosomal storage disorder resulting from inherited deficiency of ␤-glucuronidase (GUS). Mucopolysaccharidosis type VII is characterized by glycosaminoglycan storage in most tissues, including brain. In these disorders, enzyme delivery across the blood-brain barrier (BBB) is the main obstacle to correction of lysosomal storage in the CNS. Prior studies suggested mouse brain is accessible to GUS in the first 2 weeks of life but not later. To explore a possible role for the mannose 6-phosphate͞insulin-like growth factor II receptor in GUS transport across the BBB in neonatal mice, we compared brain uptake of phosphorylated GUS (P-GUS) and nonphosphorylated GUS (NP-GUS) in newborn and adult mice. 131 I-P-GUS was transported across the BBB after i.v. injection in 2-day-old mice. The brain influx rate (Kin) of 131 I-P-GUS in 2-day-old mice was 0.21 l͞g⅐min and decreased with age. By 7 weeks of age, transport of 131 I-P-GUS was not significant. Capillary depletion revealed that 62% of the 131 I-P-GUS in brain was in brain parenchyma in 2-day-old mice. In addition, uptake of 131 I-P-GUS into brain was significantly reduced by coinjection of unlabeled P-GUS or M6P in a dose-dependent manner. In contrast, the Kin of 131 I-NP-GUS (0.04 l͞g⅐min) was significantly lower than 131 I-P-GUS in 2-day-old mice. Transcardiac brain perfusion confirmed that neither 131 I-P-GUS nor 131 I-NP-GUS crossed the BBB in adult mice. These results indicate that 131 I-P-GUS transport into brain parenchyma in early postnatal life is mediated by the mannose 6-phosphate͞insulin-like growth factor II receptor. This receptor-mediated transport is not observed in adult mice.␤-glucuronidase ͉ mannose 6-phosphate͞insulin-like growth factor II receptor ͉ central nervous system ͉ lysosomal storage disease ͉ phosphorylated ␤-glucuronidase

show abstract

The putative blood-brain barrier transporter for the β-amyloid binding protein apolipoprotein j is saturated at physiological concentrations

Cited by 64 publications

References 9 publications

Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier

Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier

Triglycerides Induce Leptin Resistance at the Blood-Brain Barrier

Developmentally regulated mannose 6-phosphate receptor-mediated transport of a lysosomal enzyme across the blood-brain barrier

Contact Info

Product

Resources

About