Elevation of CSF albumin in old sheep: Relations to CSF turnover and albumin extraction at blood-CSF barrier

Albumin is the most abundant protein in both CSF and plasma, and albumin quotient is often used to assess the functions of brain barriers especially that of the blood-CSF barrier [i.e. the choroid plexus (CP) which also secretes CSF]. In this study, we took albumin as a model molecule to investigate ageing-related alterations in the CSF-CP system in sheep. We found significant ageing-related increases in the weight of lateral CP [122.4 ± 14.0 mg in the young, 198.6 ± 35.4 mg in the middle aged, 286.1 ± 25.1 mg in the old (p < 0.05)], in the CSF albumin as well as the albumin quotient. Albumin protein spots in old CSF displayed wider on 2D western immunoblotting images, and had higher densities on images of 2D large gels stained with Pro-Q Emerald 488 compared to the young samples, suggesting ageing-related post-translational modification in the albumin. CSF secretion was reduced with age: 0.148 ± 0.013 mL&min&g in the young, 0.092 ± 0.02 mL&min&g in the middle aged, 0.070 ± 0.013 mL&min&g in the old (p < 0.05). The ¹²⁵I-BSA extraction was not different among the sheep groups, nor was altered by temperature reduction, monensin, nocodazole, anti-transforming growth factor β receptor II antibody, as well as unlabelled albumins. In conclusion, elevation of albumin in old CSF is associated with reduced CSF secretion by the CP, which size increases with age. ¹²⁵I-BSA extract, reflecting the extracellular space rather than the active albumin uptake in the CP, is not different between ages. These early changes in health ageing may result in the accumulation and modifications of CSF proteins leading to neurotoxicity.