Neurobiology of Aging 32 (2011) 1338–1339 Commentary Is it appropriate to use albumin CSF/plasma ratio to assess blood brain barrier permeability? Ruo-Li Chen ∗ Pharmaceutical Science Division, King’s College London, Guy’s Campus, London Bridge, London SE1 1UL, United Kingdom Received 28 July 2008; accepted 11 August 2008 Available online 25 August 2009 Keywords: Ageing; Blood brain barrier; Albumin; CSF In their systematic review of blood brain barrier (BBB) during ageing and microvascular disease, Drs Andrew Farrall and Joanna Wardlaw summarized 31 publications on human, and concluded BBB permeability increases with normal age- ing (Farrall and Wardlaw, 2009). In the 31 publications, 8 used imaging and 23 used biochemical techniques to assess BBB permeability, in which 21 used albumin ratio of cerebrospinal fluid (CSF)/plasma. I feel that Andrew Farrall and Joanna Wardlaw have selected and analysed the data well, how- ever other interpretations have not been offered. Elevation of CSF/plasma albumin ratio has variously been interpreted as a decline in CSF secretion rate (Reiber, 1994; Silverberg et al., 2003) and/or increased permeability of brain barriers (Kleine et al., 1993) as well as isolated blood–CSF barrier dysfunction (IBD) (Brettschneider et al., 2005). CSF is mostly secreted by choroid plexuses, which are located throughout four ventricles of the brain. In humans, CSF volume is 80–150 ml and new CSF is formed at a rate of approximately 500ml per day. With increasing age, in the absence of disease, changes have been demonstrated in the choroid plexus and associated CSF circulatory system (Preston, 2001; Serot et al., 2003; Emerich et al., 2005). The rate of CSF production in healthy elderly people have been found to be half that of their younger counterparts: the mean rate of CSF production is approximately 0.41 ml min -1 for young healthy people and 0.19 ml min -1 for elderly healthy people (May et al., 1990). Brain volumes start to decrease around 40 years of age with CSF volumes start to increase accordingly (Matsumae et al., 1996). As such, CSF turn over is slower during ageing: CSF in elderly people with brain atrophy is turned over only once a day but in young healthy ∗ Tel.: +44 020 7848 6531; fax: +44 020 7848 6569. E-mail address: ronnie.chen@kcl.ac.uk. people at least 3–4 times per day (Rubenstein, 1998). Factors contributing to this reduction include increased resistance of CSF drainage into the vascular system (Albeck et al., 1998), increased thickening of the arachnoid membrane (Bellur et al., 1980) and an increased high resistance in CSF outflow due to increased central venous pressure (Rubenstein, 1998). Elevated CSF/plasma ratios have been reported for several proteins during ageing (Preston, 2001). These changes must be interpreted cautiously. Theoretically, CSF protein concen- trations should be corrected according to their age-related turn over rates to achieve same turn over rate physiological status first (Rapoport et al., 2004) before the concentra- tions can be compared logically between different ages. The increase of the albumin ratio of CSF/plasma during age- ing can not simply be interpreted as a disruption in BBB integrity. Conflict of interest No competing interest or conflict of interest. Acknowledgement Supported by The Biotechnology and Biological Sciences Research Council (BBSRC), UK. References Albeck, M.J., Skak, C., Nielsen, P.R., Olsen, K.S., Borgesen, S.E., Gjerris, F., 1998. Age dependency of resistance to cerebrospinal fluid outflow. J. Neurosurg. 89, 275–278. 0197-4580/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2008.08.024