Cellular specificity of the blood-CSF barrier for albumin transfer across the choroid plexus epithelium

PLoS One. 2014 Sep 11;9(9):e106592. doi: 10.1371/journal.pone.0106592. eCollection 2014.


To maintain the precise internal milieu of the mammalian central nervous system, well-controlled transfer of molecules from periphery into brain is required. Recently the soluble and cell-surface albumin-binding glycoprotein SPARC (secreted protein acidic and rich in cysteine) has been implicated in albumin transport into developing brain, however the exact mechanism remains unknown. We postulate that SPARC is a docking site for albumin, mediating its uptake and transfer by choroid plexus epithelial cells from blood into cerebrospinal fluid (CSF). We used in vivo physiological measurements of transfer of endogenous (mouse) and exogenous (human) albumins, in situ Proximity Ligation Assay (in situ PLA), and qRT-PCR experiments to examine the cellular mechanism mediating protein transfer across the blood-CSF interface. We report that at all developmental stages mouse albumin and SPARC gave positive signals with in situ PLAs in plasma, CSF and within individual plexus cells suggesting a possible molecular interaction. In contrast, in situ PLA experiments in brain sections from mice injected with human albumin showed positive signals for human albumin in the vascular compartment that were only rarely identifiable within choroid plexus cells and only at older ages. Concentrations of both endogenous mouse albumin and exogenous (intraperitoneally injected) human albumin were estimated in plasma and CSF and expressed as CSF/plasma concentration ratios. Human albumin was not transferred through the mouse blood-CSF barrier to the same extent as endogenous mouse albumin, confirming results from in situ PLA. During postnatal development Sparc gene expression was higher in early postnatal ages than in the adult and changed in response to altered levels of albumin in blood plasma in a differential and developmentally regulated manner. Here we propose a possible cellular route and mechanism by which albumin is transferred from blood into CSF across a sub-population of specialised choroid plexus epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Choroid Plexus / blood supply
  • Choroid Plexus / metabolism*
  • Choroid Plexus / pathology
  • Epithelium / blood supply
  • Epithelium / metabolism
  • Humans
  • Mice
  • Osteonectin / metabolism*
  • Protein Transport / genetics
  • Serum Albumin / cerebrospinal fluid
  • Serum Albumin / metabolism*


  • Osteonectin
  • SPARC protein, human
  • Serum Albumin

Grant support

The research leading to these results has received funding from the National Health and Medical Research Council (NHMRC, Australia) as part of an agreement with the European Union Seventh Framework Program (FP7/2007–2013) under grant agreement No. HEALTH-F2-2009-241778. SL was funded by an NH& MRC CJ Martin Fellowship. SL, KD, HB, H-CB, RG, AW and NS are members of the Neurobid Consortium, funded by the Seventh Framework Program (EU) and NHMRC. KM is an adviser to the Neurobid Consortium. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.