The influence of ageing in the cerebrospinal fluid concentrations of proteins that are derived from the choroid plexus, brain, and plasma

Studies have shown that ageing alone can cause increases in the concentrations of many cerebrospinal fluid (CSF) proteins. Therefore, CSF protein concentrations must be interpreted with caution before concluding that the increased concentrations of certain proteins can be used as disease-specific biomarkers. Age-related reduction in CSF turnover has been shown to have a significant concentrating effect on CSF proteins from young to old. As a result, CSF protein concentrations need to be corrected with age-specific turnovers first before performing any data comparisons between different ages. This study applied the concept of CSF/plasma concentration ratios of plasma-derived proteins that is frequently used in the investigation of brain barrier integrity to calculate the amount of protein that enters the CSF from the plasma side in different age groups. Based on our calculations, proteins with molecular weights greater than 91.92 kDa for the young, 109.51 kDa for the middle-aged and 120 kDa for the old should not be able to cross the brain barriers of the blood-brain and blood-CSF barriers to enter the CSF from the plasma side. For proteins that can be derived from the choroid plexus (CP), brain, and plasma, the amount that crosses the barriers to enter the CSF from the plasma side will contribute to their measured total protein concentrations in the CSF. CP and brain production of these proteins can be calculated when turnover corrected CSF protein concentrations are further corrected by the amount of protein that crosses the barriers. In this study, CP and brain produced concentrations of transthyretin, retinol binding protein, alpha-1-antitrypsin, gelsolin, and lactotransferrin were calculated. The production of these proteins decreased with age with alpha-1-antitrypsin protein revealing the most substantial decrease of 86% from young (0.14±0.01 mg·dL(-1)) to old (0.02 mg·dL(-1)). In conclusion, measured CSF protein concentrations for proteins that can be derived from the CP, brain, and plasma need to be corrected by age-specific CSF turnovers and by the amount of protein that crosses the brain barriers first before their concentrations can be compared logically between different ages.