Transthyretin, thyroxine, and retinol-binding protein in human cerebrospinal fluid: Effect of lead exposure

Transthyretin (TTR), synthesized by the choroid plexus, is proposed to have a role in transport of thyroid hormones in the brain. Our previous studies in animals suggest that sequestration of lead (Pb) in the choroid plexus m ay lead to a marked decrease in TTR levels in the cerebrospinal fluid (CSF) . The objectives of this study were to establish in humans whether TTR and thyroxine (T-4) are correlated in the CSF, and whether CSF levels of Pb are associated with those of TTR, T-4, and/or retinol-binding protein (RBP). E ighty-two paired CSF and blood/serum samples were collected from patients u ndergoing clinical diagnosis of CSF chemistry. Results showed that the mean value of CSF concentrations for TTR was 3.33 +/- 1.60 mug/mg of CSF protei ns (mean +/- SD, n = 82), for total T-4 (TT4) was 1.56 +/- 1.68 ng/mg (n = 82), for REP was 0.34 +/- 0.19 mug/mg (n = 82), and for Pb was 0.53 +/- 0.6 9 mug/dl (n = 61 for those above the detection limit). Linear regression an alyses revealed that CSF TTR levels were positively associated with those o f CSF TT4 (r = 0.33, p < 0.005). CSF TTR concentrations, however, were inve rsely associated with CSF Pb concentrations (P = -0.29, p < 0.05). There wa s an inverse, albeit weak, correlation between CSF TT; and CSF ph concentra tions (r = -0.22, p = 0.09). The concentrations of TTR, TT4, and Ph in the CSF did not vary as the function of their levels in blood or serum, but REP concentrations in the CSF did correlate to those of serum (r = 0.39, p < 0 .0005). Unlike TTR, CSF REP concentrations were not influenced by Ph. These human data are consistent with our earlier observations in animals, which suggest that TTR is required for thyroxine transport in the CSF and that Pb exposure is likely associated with diminished TTR levels in the CSF.