Transthyretin

TLDR

Transthyretin (TTR) is a 55‑kDa plasma protein that transports thyroxine and retinol, and its unusually high concentration in ventricular CSF implies selective transport or de novo synthesis at the blood‑CSF barrier, though its CNS role remains unclear. The study aimed to determine whether TTR is synthesized in the human choroid plexus by extending a molecular genetic approach previously used in rats. Using a cDNA clone of human TTR, the authors performed Northern blotting, in vitro translation, immunocytochemistry, and in situ hybridization on postmortem brain tissues to assess TTR mRNA and protein expression. They found abundant TTR mRNA and protein exclusively in choroid plexus epithelial cells, indicating that TTR is the first protein produced solely by the choroid plexus and suggesting a unique CNS or CSF function.

Abstract

Plasma transthyretin (TTR, formerly called prealbumin) is a 55-kd protein that participates in the plasma transport of both thyroxine and retinol (vitamin A). TTR concentrations are disproportionately high in human ventricular CSF, suggesting that TTR is either selectively transported across or synthesized de novo within the blood-CSF barrier. To address this question, we adopted a molecular genetic approach; after isolating a cDNA clone encoding human TTR, we previously demonstrated specific TTR messenger RNA (mRNA) synthesis in rat choroid plexus. We have now extended these investigations to the human brain. Northern analysis of postmortem brain homogenates revealed abundant TTR mRNA in choroid plexus, but not in cerebellum or cerebral cortex. Choroid plexus mRNA was readily translated into TTR preprotein in an in vitro translation system. An immunocytochemical survey of human postmortem brain sections revealed the presence of TTR protein specifically and uniquely in the cytoplasm of choroid plexus epithelial cells; these results were corroborated at the mRNA level by an extensive survey of whole rat-brain sections by in situ hybridization. Therefore, within the mammalian CNS, TTR is the first known protein synthesized solely by the choroid plexus, suggesting a special role for TTR in the brain or CSF. Whether this function differs from its established plasma transport functions is presently unknown.