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 may 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). Eighty-two paired 
CSF and blood/serum samples were collected from patients undergoing clinical 
diagnosis of CSF chemistry. Results showed that the mean value of CSF 
concentrations for TTR was 3.33 +/- 1.60 microg/mg of CSF proteins (mean +/- SD, 
n = 82), for total T(4) (TT(4)) was 1.56 +/- 1.68 ng/mg (n = 82), for RBP was 
0.34 +/- 0.19 microg/mg (n = 82), and for Pb was 0.53 +/- 0.69 microg/dl (n = 61 
for those above the detection limit). Linear regression analyses revealed that 
CSF TTR levels were positively associated with those of CSF TT(4) (r = 0.33, p < 
0.005). CSF TTR concentrations, however, were inversely associated with CSF Pb 
concentrations (r = -0.29, p < 0.05). There was an inverse, albeit weak, 
correlation between CSF TT(4) and CSF Pb concentrations (r = -0.22, p = 0.09). 
The concentrations of TTR, TT(4), and Pb in the CSF did not vary as the function 
of their levels in blood or serum, but RBP concentrations in the CSF did 
correlate to those of serum (r = 0.39, p < 0.0005). Unlike TTR, CSF RBP 
concentrations were not influenced by PB: 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.